OPIOIDS <406> Database EMBASE Accession Number 2005177716 Authors De Wet C.J. Reed L.J. Bearn J. Institution (De Wet, Reed, Bearn) Wickham Park House, South London and Maudsley NHS Trust, Bethlem Royal Hospital, Beckenham, Kent, United Kingdom. (Reed, Bearn) Natl. Addict. Ctr. Inst. Psychiat., London, United Kingdom. (Bearn) Wickham Park House, South London and Maudsley NHS Trust, Bethlem Royal Hospital, Monks Orchard Road, Beckenham Kent BR3 3BX, United Kingdom. Country of Publication United Kingdom Title The rise of buprenorphine prescribing in England: Analysis of NHS regional data, 2001-03. Source Addiction. 100(4)(pp 495-499), 2005. Date of Publication: Apr 2005. Abstract Aims: Since its launch in the prescribing market in 1999 for the treatment of opiate dependence, buprenorphine has rapidly become established as an alternative to methadone treatment in the United Kingdom. In the absence of evidence of its clinical superiority over methadone, and given its high relative cost, we sought to examine the impact of buprenorphine availability on opiate treatment services in England. Methods: Quarterly buprenorphine and methadone community prescription ligures were obtained for 28 Strategic Health Authorities (SHAs) in England, for the 2-year period September 2001 to September 2003. Rates of buprenorphine prescribing (as proportion of all opiate prescriptions) were examined over time by number of prescriptions and net ingredient cost. Results: Buprenorphine prescription rates increased disproportionately to methadone in all 28 SHAs. By the end of 2003 the number of buprenorphine prescriptions had increased to 23% of all opiate prescriptions, but accounted for 45% of opiate prescription costs in England. Buprenorphine prescribing rates varied substantially across different regions. Conclusions: Buprenorphine prescribing has increased dramatically and represents a disproportionately large fraction of community opiate prescribing costs. The marked regional variation suggests the need for further research and the development of national guidelines to support rational prescribing and equitable access to treatment. copyright 2005 Society for the Study of Addiction. ISSN 0965-2140 Publication Type Journal: Article Journal Name Addiction Volume 100 Issue Part 4 Page 495-499 Year of Publication 2005 Date of Publication Apr 2005 OPIOIDS <410> Database EMBASE Accession Number 2005177712 Authors Degenhardt L. Reuter P. Collins L. Hall W. Institution (Degenhardt, Collins, Hall) Natl. Drug and Alcohol Res. Centre, University of New South Wales, Sydney, NSW 2052, Australia. (Reuter) School of Public Policy, Department of Criminology, University of Maryland, United States. (Hall) Office of Public Policy and Ethics, Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD, Australia. Country of Publication United Kingdom Title Evaluating explanations of the Australian 'heroin shortage'. Source Addiction. 100(4)(pp 459-469), 2005. Date of Publication: Apr 2005. Abstract Aims: In this paper we outline and evaluate competing explanations for a heroin shortage that occurred in Australia during 2001 with an abrupt onset at the beginning of 2001. Methods: We evaluated each of the explanations offered for the shortage against evidence from a variety of sources: government reports, police and drug law enforcement documents and briefings, key informant (KI) interviews, indicator data and research data. Results: No similar shortage occurred at the same time in other markets (e.g. Vancouver, Canada or Hong Kong) whose heroin originated in the same countries as Australia's. The shortage was due most probably to a combination of factors that operated synergistically and sequentially. The heroin market had grown rapidly in the late 1990s, perhaps helped by a decline in drug law enforcement (DLE) in Australia in the early 1990s that facilitated high-level heroin suppliers in Asia to establish large-scale importation heroin networks into Australia. This led to an increase in the availability of heroin, increasingly visible street-based drug markets, increased purity and decreased price of heroin around the country. The Australian heroin market was well established by the late 1990s, but it had a low profit margin with high heroin purity, and a lower price than ever before. The surge in heroin problems led to increased funding of the Australian Federal Police and Customs as part of the National Illicit Drug Strategy in 1998-99, with the result that a number of key individuals and large seizures occurred during 1999-2000, probably increasing the risks of large-scale importation. The combination of low profits and increased success of law enforcement may have reduced the dependability of key suppliers of heroin to Australia at a time when seized heroin was becoming more difficult to replace because of reduced supplies in the Golden Triangle. These factors may have reduced the attractiveness of Australia as a destination for heroin trafficking. Conclusions: The Australian heroin shortage in 2001 was due probably to a combination of factors that included increased effectiveness of law enforcement efforts to disrupt networks bringing large shipments of heroin from traditional source countries, and decreased capacity or willingness of major traffickers to continue large scale shipments to Australia. copyright 2005 Society for the Study of Addiction. ISSN 0965-2140 Publication Type Journal: Review Journal Name Addiction Volume 100 Issue Part 4 Page 459-469 Year of Publication 2005 Date of Publication Apr 2005 OPIOIDS (A) <425> Database EMBASE Accession Number 2005172106 Authors Skoubis P.D. Lam H.A. Shoblock J. Narayanan S. Maidment N.T. Institution (Skoubis, Lam, Shoblock, Narayanan, Maidment) Dept. of Psychiat./Biobehav. Sci., Neuropsychiatric Institute, Univ. of California at Los Angeles, Los Angeles, CA 90024, United States. (Skoubis) Neuroscience Research, Global Pharmaceut. Res. and Devmt., Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, United States. (Narayanan) Glenmark Pharmaceuticals Ltd., Glenmark Research Centre, MIDC, T.T.C. Industrial Area, Navi Mumbai 400 709, India. Country of Publication United Kingdom Title Endogenous enkephalins, not endorphins, modulate basal hedonic state in mice. Source European Journal of Neuroscience. 21(5)(pp 1379-1384), 2005. Date of Publication: Mar 2005. Abstract The aversive response to naloxone administration observed in human and animal studies suggests the presence of an endogenous opioid tone regulating hedonic state but the class(es) of opioid peptides mediating such opioid hedonic tone is uncertain. We sought to address this question using mice deficient in either beta-endorphin or pro-enkephalin in a naloxone-conditioned place aversion paradigm. Mice received saline in the morning in one chamber and either saline or naloxone (0.1, 1 or 10 mg/kg, s.c.) in the afternoon in another chamber, each day for 3 days. On the test day they were given free access to the testing chambers in the afternoon and the time spent in each chamber was recorded. Whereas wildtype and beta-endorphin-deficient mice exhibited a robust conditioned place aversion to naloxone, pro-enkephalin knockout mice failed to show aversion to naloxone at any dose tested. In contrast, these mice showed a normal conditioned aversion to the kappa opioid receptor agonist, 1150,488 (5 mg/kg), and to LiCl (100 mg/kg) indicating that these mice are capable of associative learning. In a separate experiment, pro-enkephalin knockout mice, similar to wild-type and beta-endorphin-deficient mice, demonstrated a significant conditioned place preference to morphine (2.5, 5 and 10 mg/kg s.c.). These data suggest that enkephalins, but not endorphins, may mediate an endogenous opioid component of basal affective state and also indicate that release of neither endogenous enkephalins nor endorphins is critical for the acquisition or expression of the association between contextual cues and the rewarding effect of exogenously administered opiates. ISSN 0953-816X Publication Type Journal: Article Journal Name European Journal of Neuroscience Volume 21 Issue Part 5 Page 1379-1384 Year of Publication 2005 Date of Publication Mar 2005 OPIOIDS <438> Database EMBASE Accession Number 2005145216 Authors Gu J. Yao M. Wang J. Zhou W. Yang G. Liu H. Zhang Z. Liu X. Institution (Gu, Yao, Wang, Zhang, Liu) Inst. of Biochem. and Cell Biology, Shanghai Institutes for Biol. Sci., Chinese Academy of Sciences, Shanghai 200031, China. (Gu, Liu) Xinyuan Inst. of Med. and Biotech., School of Life Sciences, Zhejiang University of Sci.-Tech., Hangzhou 310018, China. (Yao) Andrus Gerontology Center, University of Southern California, Los Angeles, CA 90089, United States. (Zhou, Yang, Liu) Inst. Ningbo Addict. Res. Treatm., Ningbo 315010, China. Country of Publication United Kingdom Title Suppression of morphine withdrawal syndrome by interleukin-2 and its gene. Source NeuroReport. 16(4)(pp 387-391), 2005. Date of Publication: 15 Mar 2005. Abstract The naloxone-precipitated withdrawal syndrome in mice and rats after intrathecal injection of recombinant human interleukin-2 protein (rIL-2) or its gene was studied. The results showed that rIL-2 could significantly decrease the number of jumps in mice. In rats, rIL-2 significantly suppressed irritating, diarrhea, weight loss, abnormal posture and salivation. Tendencies towards reductions in teeth chewing and dog-shaking were also observed. Furthermore, pcDNA3-IL-2 (8 mug DNA) had a similar effect as 1 x 10<sup>4</sup> IU rIL-2 protein on inhibition of morphine withdrawal syndrome in mice, and the expression of rIL-2 protein in spinal cord could be detected for 6 days. These findings provided further evidence for the neuroregulatory function of an immunological molecule such as IL-2. copyright 2005 Lippincott Williams & Wilkins. ISSN 0959-4965 Publication Type Journal: Article Journal Name NeuroReport Volume 16 Issue Part 4 Page 387-391 Year of Publication 2005 Date of Publication 15 Mar 2005 OPIOIDS <439> Database EMBASE Accession Number 2005143487 Authors Gabra B.H. Afify E.A. Daabees T.T. Abou Zeit-Har M.S. Institution (Gabra) Inst. of Pharmacology of Sherbrooke, School of Medicine, University of Sherbrooke 3001, 12E Avenue Nord, Sherbrooke, Que. J1H5N4, Canada. (Afify, Daabees, Abou Zeit-Har) Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt. Country of Publication United Kingdom Title The role of the NO/NMDA pathways in the development of morphine withdrawal induced by naloxone in vitro. Source Pharmacological Research. 51(4)(pp 319-327), 2005. Date of Publication: Apr 2005. Abstract The effect of nitric oxide (NO)/N-methyl-d-aspartate (NMDA) pathways on naloxone-induced withdrawal contracture was studied in vitro in a model of acute morphine dependence in the isolated guinea pig ileum. Exposure of the isolated guinea pig ileum to morphine (10<sup>5</sup> M) for 5 min resulted in acute dependence, characterized by a strong withdrawal contracture induced by naloxone (5 x 10<sup>-5</sup> M). The NO synthase (NOS) inhibitor N <sup>G</sup>-nitro-l-arginine methyl ester (l-NAME; 5 x 10<sup>-4</sup> M) as well as the soluble guanylate cyclase inhibitor methylene blue (MB; 10 muM) were found to significantly attenuate the naloxone-induced withdrawal contracture. In addition, the NO precursor l-arginine (5 x 10<sup>-4</sup> M) as well as the NO donors sodium nitroprusside (SNP; 1 muM) and sodium azide (NaZ; 10 muM) were able to revert the effect of l-NAME returning the amplitude of naloxone-induced contracture to the same level in control morphine-dependent ilea. We also demonstrated that the competitive NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (AP-5; 50 muM) potently reduced the amplitude of naloxone-induced contracture in the same model, an effect that was reversed by co-administration of the excitatory amino acid l-glutamate (40 muM). This in vitro study confirms the implication of the NO/NMDA pathways in morphine dependence. copyright 2004 Elsevier Ltd. All rights reserved. ISSN 1043-6618 Publication Type Journal: Article Journal Name Pharmacological Research Volume 51 Issue Part 4 Page 319-327 Year of Publication 2005 Date of Publication Apr 2005 OPIOIDS (A) <465> Database EMBASE Accession Number 2005120481 Authors Grasing K. He S. Institution (Grasing, He) Substance Abuse Research Laboratory, Kansas City Vet. Aff. Medical Center, 4801 Linwood Boulevard, Kansas City, MO, United States. (Grasing) Division of Clinical Pharmacology, Department of Medicine, Univ. of Kansas School of Medicine, Kansas City, MO, United States. (Grasing) Research Service, 151, 4801 Linwood Boulevard, Kansas City, MO 64128, United States. Country of Publication United Kingdom Title Effects of high-dose selegiline on morphine reinforcement and precipitated withdrawal in dependent rats. Source Behavioural Pharmacology. 16(1)(pp 1-13), 2005. Date of Publication: Feb 2005. Abstract Selegiline is an irreversible inhibitor of monoamine oxidase (MAO) with psychostimulant and neuroprotective effects. Several lines of evidence suggest that treatment with selegiline at doses that exceed levels required for inhibition of MAO can produce distinct pharmacologic effects. The purpose of this study was to evaluate the effects of chronic treatment with highdose selegiline on extinction responding, cue-induced reinstatement, morphine reinforcement and naloxone-precipitated withdrawal. After pretreatment with noncontingent morphine to establish opiate dependence, rats acquired self-administration of 3.2 mg/kg per injection of morphine under a progressive ratio schedule. Daily treatment with saline or 6.4 mg/kg per day of selegiline was then administered over extinction, reinstatement and re-acquisition of morphine self-administration. To enhance or diminish the potential for psychostimulant effects, selegiline was administered either immediately prior to (pre-session) or 1 h following (post-session) extinction, reinstatement and; self-administration sessions. Pre-session selegiline decreased the number of ratios completed on days 2, 3 and 4 of extinction, and decreased morphine self-administration during all four re-acquisition sessions. When administered at the same dose level, post-session selegiline decreased responding on the fourth extinction session, and was ineffective in modifying re-acquisition of self-administration. Selegiline administered by either schedule did not modify cue-induced reinstatement. Daily treatment with 6.4 mg/kg per day of selegiline did not modify self-administration of food under a progressive ratio schedule. Acute treatment with single, 6.4 mg/kg doses of selegiline attenuated naloxone-induced increases in ptosis and global withdrawal score, but did not modify any other sign of withdrawal or global withdrawal score calculated without ratings of ptosis. In conclusion, high-dose selegiline can attenuate extinction responding and morphinereinforced behavior, and these effects may be mediated by psychostimulant metabolites. copyright 2005 Lippincott Williams & Wilkins. ISSN 0955-8810 Publication Type Journal: Article Journal Name Behavioural Pharmacology Volume 16 Issue Part 1 Page 1-13 Year of Publication 2005 Date of Publication Feb 2005 OPIOIDS <467> Database EMBASE Accession Number 2005115753 Authors Porzionato A. Macchi V. Guidolin D. Parenti A. Ferrara S.D. De Caro R. Institution (Macchi, Guidolin, De Caro) Dept. of Hum. Anatomy and Physiology, Section of Anatomy, University of Padova, Padova, Italy. (Parenti) Dept. of Oncological and Surg. Sci., Section of Pathologic Anatomy, University of Padova, Padova, Italy. (Porzionato, Ferrara) Environ. Medicine and Public Health, Section of Legal Medicine, University of Padova, Padova, Italy. (De Caro) Dept. of Hum. Anatomy and Physiology, Section of Anatomy, Via A. Gabelli 65, 35121 Padova, Italy. Country of Publication United Kingdom Title Histopathology of carotid body in heroin addiction. Possible chemosensitive impairment. Source Histopathology. 46(3)(pp 296-306), 2005. Date of Publication: Mar 2005. Abstract Aims: To perform a morphometric analysis of carotid bodies in opiate addicts. Methods and results: Carotid bodies were sampled at autopsy from 35 subjects who died of heroin intoxication (mean age 26 years), and from eight young (22 years) and eight older subjects (66.5 years) who died of trauma. Sections were stained with haematoxylineosin, azanMallory, and double-labelling immunohistochemistry with antineuronal specific enolase and anti-S100, to count type I and type II cells. Interlobular and intralobular connective tissue was increased both in the opiate cases (43.45 +/- 6.79%, P < 0.001. and 13.34 +/- 5.72%, P < 0.001, respectively) and older cases (46.67 +/- 1.65%, P < 0.001, and 9.62 +/- 2.11%, P < 0.05, respectively) compared with young cases (33.17 +/- 6.41% and 4.33 +/- 1.84%, respectively). The percentage of type II cells in the opiate cases (51.6 +/- 7.3%, P < 0.001) and in the older controls (49.0 +/- 7.2%, P < 0.01) was higher than in the young cases (37.9 +/- 3.0%). Among type I cells, the light cell percentage in the opiate cases (65.85 +/- 11%, P < 0.001) was reduced with respect to the two control groups (82.8 +/- 5.34%, young: 81.62 +/8.58%, older). Conclusions: The increases in connective tissue and type II cells are similar to findings in ageing and chronic pulmonary disease, and may be ascribed to glomic hypoxia. A direct action of opiates should be taken into account for the decrease in light cells in heroin addiction. The histopathological changes in the carotid body, by impairing chemosensivity, may play a role in the fatal cardiorespiratory derangement of heroin addicts. copyright 2005 Blackwell Publishing Limited. ISSN 0309-0167 Publication Type Journal: Article Journal Name Histopathology Volume 46 Issue Part 3 Page 296-306 Year of Publication 2005 Date of Publication Mar 2005 OPIOIDS <468> Database EMBASE Accession Number 2005114955 Authors Sorensen H.J. Jepsen P.W. Haastrup S. Juel K. Institution (Sorensen) Danish Epidemiology Science Centre, Institute of Preventive Medicine, Copenhagen Hospital Corporation, Copenhagen, Denmark. (Sorensen) Department of Psychiatry, Copenhagen University Hospital, Amager, Denmark. (Jepsen) Department of Psychiatry, Copenhagen University Hospital, Rigshospitalet, (Haastrup) Department of Psychiatry, Copenhagen University Hospital, Glostrup, Denmark. (Juel) National Institute of Public Health, Copenhagen, Denmark. (Jepsen) Dist. Mental Health Centre Indre By, Vestergade 27, DK-1456 Copenhagen K, Denmark. Country of Publication United Kingdom Title Drug-use pattern, comorbid psychosis and mortality in people with a history of opioid addiction. Source Acta Psychiatrica Scandinavica. 111(3)(pp 244-249), 2005. Date of Publication: Mar 2005. Abstract Objective: To compare the 15-year mortality of people with a history of opioid dependence that had achieved stable abstinence, with the mortality associated with continued drug use. Another objective was to study the influence of hospitalization with comorbid psychosis on the 15-year mortality. Method: In 1984, 188 persons (122 men and 66 women) with a history of intravenous narcotics addiction were interviewed about their drug-use pattern. A registrybased follow-up continued through 1999 and mortality was assessed. Three 1984-drug-use categories were formed. In category 1, cohort members had achieved stable abstinence from drug use by 1984. Using Cox multiple regression analysis, we (i) estimated reduced mortality of category 1 drug users, and (ii) studied the influence of hospitalization with comorbid psychosis on mortality. Results: About 32% had died during the 15-year follow-up. The 15year mortality associated with stable abstinence was reduced by 56% when compared with the perceived worst drug-use pattern. Hospitalization for comorbid psychosis was not independently associated with mortality in this sample. When drug-use categories were compared with mortality expectations for the general population, the standard mortality rates (SMRs) were clearly elevated. Even in the stably abstinent drug-use category (category 1), SMR was significantly elevated by at least seven-fold in both genders. Conclusion: People who had achieved stable abstinence from injecting narcotics use were at lower risk of premature death than people with continued drug use. A residual observed excess mortality in people who had apparently achieved stable abstinence from drug use is consistent with the view of drug addiction as a chronic disease. copyright Blackwell Munksgaard 2004. ISSN 0001-690X Publication Type Journal: Article Journal Name Acta Psychiatrica Scandinavica Volume 111 Issue Part 3 Page 244-249 Year of Publication 2005 Date of Publication Mar 2005 OPIOIDS <472> Database EMBASE Accession Number 2005103102 Authors Jage J. Institution (Jage) Department of Anaesthesiology, University Hospital, Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Country of Publication United Kingdom Title Opioid tolerance and dependence - Do they matter? Source European Journal of Pain. 9(2 SPEC. ISS.)(pp 157-162), 2005. Date of Publication: Apr 2005. Abstract The use of opioids has long been accepted as the standard of care in patients with cancer and acute pain. Opioids can further be used effectively in specific subgroups of patients with chronic nonmalignant pain states. While the development of tolerance and physical dependence are known effects of opioids in cancer and noncancer pain populations, these patients can not be regarded as addicted. However, long-term therapy with short-acting opioids predisposes to tolerance and addiction. Recent research has confirmed the important role of psychopathologic and psychosocial conditions as predictors of failed opioid effectiveness in a significant number of noncancer pain subgroups. The clinical picture of failed therapy may be complicated by noncompliance, concealed consumption of psychotropic substances, and diversion of prescribed opioids for various purposes as, e.g., selling for profit, or sharing excess opioids with others. This article discusses the effects of opioid therapy, including tolerance, physical dependence, drug-aberrant behavior, drug history, psychopathology, and somatization. copyright 2004 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. ISSN 1090-3801 Publication Type Journal: Article Journal Name European Journal of Pain Volume 9 Issue Part 2 SPEC. ISS. Page 157-162 Year of Publication 2005 Date of Publication Apr 2005 OPIOIDS <474> Database EMBASE Accession Number 2005093533 Authors Aldhous P. Country of Publication United Kingdom Title Cold turkey, Vietnamese style. Source Nature. 433(7026)(pp 568-569), 2005. Date of Publication: 10 Feb 2005. Abstract It was invented by a healer familiar with the horrors of opiate addiction, and refined by Vietnam's leading chemistry lab. Can this novel herbal cocktail ease withdrawal and reduce drug cravings? Peter Aldhous investigates. ISSN 0028-0836 Publication Type Journal: Short Survey Journal Name Nature Volume 433 Issue Part 7026 Page 568-569 Year of Publication 2005 Date of Publication 10 Feb 2005 OPIOIDS <477> Database EMBASE Accession Number 2005088328 Authors Shewan D. Dalgarno P. Institution (Shewan, Dalgarno) Glasgow Caledonian University, Glasgow, United Kingdom. (Shewan) Department of Psychology, Glasgow Caledonian University, City Campus, Cowcaddens Road, Glasgow G4 0BA, United Kingdom. Country of Publication United Kingdom Title Evidence for controlled heroin use? Low levels of negative health and social outcomes among non-treatment heroin users in Glasgow (Scotland). Source British Journal of Health Psychology. 10(1)(pp 33-48), 2005. Date of Publication: Feb 2005. Abstract Objectives. This longitudinal study focused on 126 long-term heroin users who had never been in specialist treatment for use of any drug. The primary aim of the study was to assess whether this 'hidden' population resembled heroin users identified with drug treatment agencies, or alternatively, to test whether heroin could indeed be used in a controlled, nonintrusive fashion for an extended period of time. Design and methods. Recruitment was achieved through chain-referred purposive sampling methods, and data were collected through two semi-structured interviews. 67% of participants were re-recruited for follow-up. Results. Participants had levels of occupational status and educational achievement comparable to that in the general UK population, and considerably higher than typically found in heroin research. At the conclusion of the study, six participants had entered treatment. While there was evidence of intensive risky patterns of drug use among the sample, there was equal evidence for planned, controlled patterns of use. Some drug-related negative health and social outcomes had occurred on a lifetime basis, but ongoing problems were rare, and heroin was not a significant predictor in either context. In contrast to typical samples of heroin users, high levels of negative health and social outcomes did not appear to be inevitable within this sample. Frequency of heroin use was predicted by attributional items, indicating the importance of psychological factors in drug use and addiction. Conclusions. Drug research should more fully incorporate previously hidden populations to more fully inform theory and practice. The pharmacological properties of specific substances should not be assumed to inevitably lead to addictive and destructive patterns of drug use. ISSN 1359-107X Publication Type Journal: Article Journal Name British Journal of Health Psychology Volume 10 Issue Part 1 Page 33-48 Year of Publication 2005 Date of Publication Feb 2005 OPIOIDS <478> Database EMBASE Accession Number 2005083929 Authors De Jong C.A.J. Laheij R.J.F. Krabbe P.F.M. Institution (De Jong) Novadic - Kentron - Netwk. A., Nijmegen Inst. S., Radboud University Nijmegen, Nijmegen, Netherlands. (Laheij, Krabbe) Dept. of Med. Technology Assessment, University Medical Centre Nijmegen, Nijmegen, Netherlands. (De Jong) Novadic - Kentron - Netwk. A., Nijmegen Inst. S., Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, Netherlands. Country of Publication United Kingdom Title General anaesthesia does not improve outcome in opioid antagonist detoxification treatment: A randomized controlled trial. Source Addiction. 100(2)(pp 206-215), 2005. Date of Publication: Feb 2005. Abstract Aim: Opioid detoxification by administering opioid-antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without anaesthesia. Design: Randomized controlled open clinical trial from September 1999 to August 2001. Setting: Four addiction centres in collaboration with three general hospitals in the Netherlands. Participants: A total of 272 opioid-dependent patients whose previous attempts to abstain were unsuccessful. Intervention: Patients received rapid detoxification with general anaesthesia (RD-GA) or without general anaesthesia (RD). Measurements: Urine screens and an interview (EuropASI) to assess opioid abstinence two questionnaires (SOOS, OOWS) to measure withdrawal symptoms and one to measure craving (VAS). Findings: One month after the intervention 62.8% of the patients in the RD-GA group and 60.0% in the RD group were abstinent for opioids (P = 0.71). No adverse events or complications occurred during RD; however, in the RD-GA group, five adverse events necessitated admission to a general hospital. The average 1month cost for RD was [euro]2517 versus [euro]4439 for RD-GA. Conclusions: Rapid detoxification under general anaesthesia did not result in higher levels of opioid abstinence than rapid detoxification without anaesthesia. The cost of the former intervention was much higher. ISSN 0965-2140 Publication Type Journal: Article Journal Name Addiction Volume 100 Issue Part 2 Page 206-215 Year of Publication 2005 Date of Publication Feb 2005 OPIOIDS <481> Database EMBASE Accession Number 2005079225 Authors Simoens S. Matheson C. Bond C. Inkster K. Ludbrook A. Institution (Simoens) Drug and Patient Information, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Edward van Evenstraat 4, 3000 Leuven, Belgium. (Matheson, Bond, Inkster) Dept. of Gen. Practice/Primary Care, University of Aberdeen, Aberdeen, United Kingdom. (Ludbrook) Health Economics Research Unit, University of Aberdeen, Aberdeen, United Kingdom. Country of Publication United Kingdom Title The effectiveness of community maintenance with methadone or buprenorphine for treating opiate dependence. Source British Journal of General Practice. 55(511)(pp 139-146), 2005. Date of Publication: Feb 2005. Abstract Background. Opiate dependence is a major health and social issue in many countries. A mainstay of therapy has been methadone maintenance treatment, but other treatments, particularly buprenorphine, are increasingly being considered. Aim. To conduct a systematic review to synthesise and critically appraise the evidence on the effectiveness of community maintenance programmes with methadone or buprenorphine in treating opiate dependence. Method. A systematic review of databases, journals and the grey literature was carried out from 1990-2002. Inclusion criteria were: community-based, randomised controlled trials of methadone and/or buprenorphine for opiate dependence involving subjects who were aged 18 years old or over. Results. Trials were set in a range of countries, employed a variety of comparators, and suffered from a number of biases. The evidence indicated that higher doses of methadone and buprenorphine are associated with better treatment outcomes. Low-dose methadone (20 mg per day) is less effective than buprenorphine (2-8 mg per day). Higher doses of methadone (>50-65 mg per day) are slightly more effective than buprenorphirie (2-8 mg per day). There was some evidence that primary care could be an effective setting to provide this treatment, but such evidence was sparse. Conclusion. The literature supports the effectiveness of substitute prescribing with methadone or buprenorphine in treating opiate dependence. Evidence is also emerging that the provision of methadone or buprenorphine by primary care physicians is feasible and may be effective. copyright British Journal of General Practice 2005. ISSN 0960-1643 Publication Type Journal: Review Journal Name British Journal of General Practice Volume 55 Issue Part 511 Page 139-146 Year of Publication 2005 Date of Publication Feb 2005 OPIOIDS (A) <484> Database EMBASE Accession Number 2005069433 Authors Rasmussen K. Martin H. Berger J.E. Seager M.A. Institution (Rasmussen, Seager) Lilly Research Laboratories, Eli Lilly and Co., Lilly Corporate Center, Indianapolis, IN 46285, United States. (Martin, Berger) Coll. of Pharm. and Health Sciences, Butler University, Indianapolis, IN 46028, United States. Country of Publication United Kingdom Title The mGlu5 receptor antagonists MPEP and MTEP attenuate behavioral signs of morphine withdrawal and morphine-withdrawal-induced activation of locus coeruleus neurons in rats. Source Neuropharmacology. 48(2)(pp 173-180), 2005. Date of Publication: Feb 2005. Abstract N-Methyl-D-aspartate (NMDA) antagonists have been demonstrated to suppress the signs of opiate withdrawal; however, side effects limit their clinical use. Since the metabotropic glutamate (mGlu) 5 receptor has been shown to affect glutamate release and modulate NMDA receptor function, we examined the effects of two selective mGlu5 receptor antagonists, 2-methyl-6-(phenyl-ethynyl)- pyridine (MPEP) and 3-[(2-methyl-1,3-thiazol-4yl)ethynyl]pyridine (MTEP), on morphine withdrawal. Pretreatment with MPEP or MTEP (1, 3, and 10 mg/kg, i.p.) significantly attenuated behavioral signs of morphine withdrawal. Specifically, both MPEP and MTEP attenuated the occurrence/severity of chews, digging, salivation, and weight loss, and increased the occurrence of erections. Neither compound changed the occurrence of wet-dog shakes, ptosis, irritability, or lacrimation. Both MPEP and MTEP produced a modest, but significant, attenuation of morphine-withdrawal-induced activation of locus coeruleus neurons in anesthetized rats. These results indicate a role for mGlu5 receptors in morphine withdrawal and suggest the potential for mGlu5 antagonists in the treatment of withdrawal from opiates and other drugs of abuse. copyright 2004 Elsevier Ltd. All rights reserved. ISSN 0028-3908 Publication Type Journal: Article Journal Name Neuropharmacology Volume 48 Issue Part 2 Page 173-180 Year of Publication 2005 Date of Publication Feb 2005 OPIOIDS <489> Database EMBASE Accession Number 2005051472 Authors Larrinaga G. Gil J. Meana J.J. Ruiz F. Callado L.F. Irazusta J. Institution (Larrinaga) Department of Nursing I, University of the Basque Country, Leioa, P.O. Box 699, E-48940 Bilbao, Bizkaia, Spain. (Gil, Ruiz, Irazusta) Department of Physiology, University of the Basque Country, Spain. (Meana, Callado) Department of Pharmacology, University of the Basque Country, Spain. Country of Publication United Kingdom Title Aminopeptidase activity in the postmortem brain of human heroin addicts. Source Neurochemistry International. 46(3)(pp 213-219), 2005. Date of Publication: Feb 2005. Abstract Several studies have reported that the chronic administration of opioids induces changes in the biosynthesis of endogenous opioid peptides or their precursors in specific brain regions of the adult central nervous system. However, little is known about the catabolic regulation of opioid peptides and its contribution to neuroadaptative changes underlying drug addiction. In the present study, we have analyzed the activity of two enkephalin-degrading enzymes (puromycin-sensitive aminopeptidase or PSA and aminopeptidase N or APN) and two functionally different, soluble aminopeptidases (aminopeptidase B and aspartylaminopeptidase) in postmortem samples of prefrontal cortex and caudate nucleus of eight human heroin addict brains and eight matched-controls. Enzyme activities were fluorimetrically measured using beta-naphthylamide derivatives. An increase in the activity of soluble PSA in the prefrontal cortex of heroin abusers was observed (heroin addict group: 51,452 +/- 3892 UAP/mg protein versus control group: 42,003 +/- 2597 UAP/mg protein; P < 0.05), while the activity of the other peptidases in both brain regions remained unaltered. This result agrees with previous findings in morphine-tolerant rats, and indicates that soluble PSA may be involved in neurobiological processes which underlie heroin addiction. copyright 2004 Elsevier Ltd. All rights reserved. ISSN 0197-0186 Publication Type Journal: Article Journal Name Neurochemistry International Volume 46 Issue Part 3 Page 213-219 Year of Publication 2005 Date of Publication Feb 2005 OPIOIDS <491> Database EMBASE Accession Number 2005050645 Authors Damen K.F.M. Dejong C.A.J. Breteler M.H.M. Vanderstaak C.P.F. Institution (Damen, Dejong, Breteler, Vanderstaak) Nijmegen Inst. Sci. Practitioners, Montessorilaan 10, 6525 HR Nijmegen, Netherlands. Country of Publication United Kingdom Title Construct validity of the SIDP-IV in an opioid-dependent patient sample. Source Journal of Substance Use. 10(1)(pp 1-9), 2005. Date of Publication: Feb 2005. Abstract Aims: Studies on opioid-dependent patients, report high comorbidity with personality pathology. Since psychiatric comorbidity is related to poorer treatment outcome and drop-out in opioid-dependent patients, in this study, the underlying structure of the DSM-IV personality disorders in an opioid-dependent patient sample (n=263), assessed by the structured interview for DSM-IV Personality, was explored in order to contribute to the construct validity of this instrument. Design: Explorative factor analysis yielded a three-factor solution, largely resembling the DSM-IV cluster model. Findings: The optional disorders, depressive and negativistic personality disorder, did not detract from the presumed model. Confirmatory factor analysis did not confirm a good fit of the model to the data, which is due to the paranoid personality disorder (PD) which groups with cluster B PDs. Conclusions: Overall, the underlying structure of DSM-IV PDs resembles the presumed DSM-IV cluster model, thereby suggesting good construct validity of the SIDP-IV in opioid-dependent patients. copyright 2005 Taylor & Francis Group Ltd. ISSN 1465-9891 Publication Type Journal: Article Journal Name Journal of Substance Use Volume 10 Issue Part 1 Page 1-9 Year of Publication 2005 Date of Publication Feb 2005 OPIOIDS <495> Database EMBASE Accession Number 2005048575 Authors Ammon-Treiber S. Hollt V. Institution (Ammon-Treiber, Hollt) Inst. of Pharmacology and Toxicology, Otto-von-Guericke University, Magdeburg, Germany. (Ammon-Treiber) Inst. of Pharmacology and Toxicology, Otto-von-Guericke Univ. Magdeburg, Leipziger Str. 44, D39120 Magdeburg, Germany. Country of Publication United Kingdom Title Morphine-induced changes of gene expression in the brain. Source Addiction Biology. 10(1)(pp 81-89), 2005. Date of Publication: Mar 2005. Abstract Repeated opiate administration alters gene expression in different brain regions of rodents, an effect which may contribute to plastic changes associated with addictive behaviour. There is increasing evidence that multiple transcription factors are induced in morphine tolerance, sensitization and during morphine withdrawal. Whereas morphine treatment does not lead to major alterations in the expression of mu-opioid receptors (MOR), there is transcriptional regulation of proteins involved in MOR trafficking such as GRK2 or beta arrestin 2 as well as altered expression of other receptors such as dopamine receptors, NMDA receptors, GABA<sub>A</sub> receptor and alpha <sub>2A</sub> adrenoceptor. Recent gene expression profiling studies reveal additional clusters of morphine-responsive genes: whereas single dose administration has been shown to predominantly reduce expression of genes involved in metabolic function, ascending morphine doses leading to morphine tolerance revealed induction of genes which alter patterns of synoptic connectivity such as arc or ania3. These genes remained elevated after precipitated withdrawal, which also triggered the expression of several transcriptional activators and repressors. In addition, morphine has been shown to be a strong inducer of heat shock protein 70, a cell protective protein which might counter-regulate opiate-induced neurotoxicity. Temporal expression profiles during a chronic morphine application schedule revealed discrete and fluctuating expression of gene clusters such as transcription factors, G-protein-coupled receptors and neuropeptides. Prolonged abstinence seems to be characterized by up-regulation of several transcription factors and persistent down-regulation of ligand gated ion channels such as glutamatergic and GABA-ergic receptor subunits. These long-term changes in receptor expression suggest a persistent alteration of synaptic signalling after morphine treatment. ISSN 1355-6215 Publication Type Journal: Article Journal Name Addiction Biology Volume 10 Issue Part 1 Page 81-89 Year of Publication 2005 Date of Publication Mar 2005 OPIOIDS (A) <497> Database EMBASE Accession Number 2005039578 Authors Wang Y. Wan C. Zhou W. Peng T. Liu Y. Wang Z. Li G. Cornelisson G. Halberg F. Institution (Liu, Wang, Wan, Zhou, Peng, Liu, Wang) West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, China. (Li) Nanchong Central Hospital, Nanchong, Sichuan 637000, China. (Cornelisson, Halberg) Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN 55455, United States. Country of Publication United Kingdom Title The role of mPer1 in morphine dependence in mice. Source Neuroscience. 130(2)(pp 383-388), 2005. Date of Publication: 2005. Abstract Investigations using Drosophila melanogaster have shown that the circadian clock gene period can influence behavioral responses to cocaine, and the mouse homologues, mPer1 and mPer2, modulate cocaine sensitization and reward. In the present study, we applied DNAzyme targeting mPer1 to interfere the expression of mPer1 in CNS in mice and studied the role of mPer1 on morphine dependence. We found that the DNAzyme could attenuate the expression of mPer1 in CNS in mice. Mice treated with DNAzyme and morphine synchronously did not show preference to the morphine-trained side, whereas the control group did. In contrast, mice treated with DNAzyme after morphine showed preference to the morphine-trained side as well as the control group did. These results indicate that drug dependence seems to be influenced at least partially by mPer1, but mPer1 cannot affect morphine dependence that has been formed. copyright 2004 IBRO. Published by Elsevier Ltd. All rights reserved. ISSN 0306-4522 Publication Type Journal: Article Journal Name Neuroscience Volume 130 Issue Part 2 Page 383-388 Year of Publication 2005 Date of Publication 2005 OPIOIDS <500> Database EMBASE Accession Number 2005038698 Authors Bailey C.P. Connor M. Institution (Bailey) Department of Pharmacology, University of Bristol, School of Medical Sciences, Bristol BS8 1TD, United Kingdom. (Connor) Pain Management Research Institute, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia. Country of Publication United Kingdom Title Opioids: Cellular mechanisms of tolerance and physical dependence. Source Current Opinion in Pharmacology. 5(1)(pp 60-68), 2005. Date of Publication: Feb 2005. Abstract Morphine and other opioids are used and abused for their analgesic and rewarding properties. Tolerance to these effects develops over hours/days to weeks, as can physical and psychological dependence. Despite much investigation, the precise cellular mechanisms underlying opioid tolerance and dependence remain elusive. Recent studies examining muopioid receptor desensitization and trafficking have revealed several potential mechanisms for acute receptor regulation. Other studies have reported changes in many other proteins that develop during chronic opioid treatment or withdrawal and such changes may be partly responsible for the cellular and synaptic adaptations to prolonged opioid exposure. W hile these studies have added to our knowledge of the cellular processes participating in opioid tolerance and dependence, the challenge remains to integrate these observations into a coherent explanation of the complex changes observed in whole animals chronically exposed to opioids. copyright 2005 Elsevier Ltd. All rights reserved. ISSN 1471-4892 Publication Type Journal: Review Journal Name Current Opinion in Pharmacology Volume 5 Issue Part 1 Page 60-68 Year of Publication 2005 Date of Publication Feb 2005 OPIOIDS <512> Database EMBASE Accession Number 2005006546 Authors Greenwald M.K. Roehrs T.A. Institution (Greenwald) Substance Abuse Research Division, Dept. of Psychiat./Behav. Neurosci., Wayne State Univ. School of Medicine, Detroit, MI, United States. (Roehrs) Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, United States. (Greenwald) Substance Abuse Research Division, Dept. of Psychiat./Behav. Neurosci., Wayne State University, 2761 E Jefferson Ave, Detroit, MI 48207, United States. Country of Publication United Kingdom Title Mu-opioid self-administration vs passive administration in heroin abusers produces differential EEG activation. Source Neuropsychopharmacology. 30(1)(pp 212-221), 2005. Date of Publication: Jan 2005. Abstract Psychoactive drug self-administration (SA) produces different neurobiological effects than passive administration (PA) in non-human animals; however, such consequences have never been examined in human drug abusers. The present study compared electroencephalographic (EEG) activation produced by intravenous PA and SA of the muopioid fentanyl in eight heroin-dependent, methadone-stabilized male participants. In phase 1, participants received cumulative PA of fentanyl (up to 1.5mg/70kg; session 1), then bolus PA of placebo and fentanyl 1.5mg/70kg (session 2), High-dose fentanyl significantly increased the amplitude of slow-frequency (delta- and theta-band) EEG activity. In phase 2, bolus fentanyl 1.5 mg/70kg was available for SA, requiring the participant to complete 1500 responses, in each of two sessions after saline or naloxone pretreatment Delta EEG peak amplitude increases were greater following fentanyl SA than fentanyl PA, primarily over the central midline region, and were attenuated by naloxone pretreatment. The EEG increase and its attenuation by naloxone agree with preclinical evidence and suggest that SA-related EEG responses were mediated by opioid receptors. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 30 Issue Part 1 Page 212-221 Year of Publication 2005 Date of Publication Jan 2005 OPIOIDS (A) <513> Database EMBASE Accession Number 2005006535 Authors Narita M. Kishimoto Y. Ise Y. Yajima Y. Misawa K. Suzuki T. Institution (Narita, Kishimoto, Ise, Yajima, Misawa, Suzuki) Department of Toxicology, Hoshi Univ. Sch. Pharm./P. S., Ebara, Shinagawa-ku, Tokyo, Japan. (Ise) Department of Pharmaceutical Service, Nippon Medical School Hospital, Sendagi Bunkyo-ku, Tokyo, Japan. (Misawa) Narcotic Drugs/Psychotropic S. E. D., World Health Organization, Geneva, Switzerland. (Narita, Suzuki) Department of Toxicology, Hoshi Univ. Sch. of Pharm./P. S., 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. Country of Publication United Kingdom Title Direct evidence for the involvement of the mesolimbic kappa-opioid system in the morphine-induced rewarding effect under an inflammatory pain-like state. Source Neuropsychopharmacology. 30(1)(pp 111-118), 2005. Date of Publication: Jan 2005. Abstract Recent clinical studies have demonstrated that when morphine is used to control pain in cancer patients, psychological dependence is not a major concern. The present study was undertaken to ascertain the modulation of psychological dependence on morphine under a chronic pain-like state in rats. The prototypical mu-opioid receptor agonist morphine (8 mg/kg, i.p.) induced a dose-dependent place preference. In the present study, we found that an inflammatory pain-like state following formalin injection significantly suppressed the morphineinduced rewarding effect. This effect was almost reversed by s.c. pretreatment with the kappa-opioid receptor antagonist norbinaltorphimine (nor-BNI, 5 mg/kg). Furthermore, the morphine-induced increase in dopamine (DA) turnover in the limbic forebrain was significantly inhibited by treatment with formalin. This inhibition was also suppressed by pretreatment with nor-BNI. In addition, in vivo microdialysis studies clearly showed that the morphine-induced increase in the extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in the nucleus accumbens (N.Acc.) was significantly decreased in rats that had been pretreated with formalin. This effect was in turn reversed by the microinjection of a specific dynorphin A antibody into the N.Acc. These findings suggest that the inflammatory pain-like state induced by formalin injection may have caused a sustained activation of the kappa-opioidergic system within the N.Acc., resulting in suppression of the morphine-induced rewarding effect in rats. The present study provides further evidence of the clinical usefulness of morphine in patients suffering from severe pain. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 30 Issue Part 1 Page 111-118 Year of Publication 2005 Date of Publication Jan 2005 OPIOIDS (A) <514> Database EMBASE Accession Number 2005006534 Authors Lopez-Fando A. Rodriguez-Munoz M. Sanchez-Blazquez P. Garzon J. Institution (Lopez-Fando, Rodriguez-Munoz, Sanchez-Blazquez, Garzon) Neurofarmacologia, Inst. Neurbio. Santiago Ramon Cajal, CSIC, Madrid, Spain. (Garzon) Neurofarmacologia, Instituto Cajal, Consejo Sup. de Invest. Cientificas, Avd Doctor Arce, 37, Madrid E28002, Spain. Country of Publication United Kingdom Title Expression of neural RGS-R7 and Gbeta5 proteins in response to acute and chronic morphine. Source Neuropsychopharmacology. 30(1)(pp 99-110), 2005. Date of Publication: Jan 2005. Abstract The R7 subfamily of regulators of G-protein signaling (RGS) proteins (RGS6, RGS7, RGS92, and RGS11), and its binding protein Gbeta5, are found in neural structures of mouse brain. A single intracerebroventricular priming dose of 10 nmol morphine gave rise to acute tolerance to the analgesic effects of successive identical test doses of the opioid. At 2 h after administering the acute opioid, RGS7 mRNA levels in the striatum plus those of RGS9-2 in the striatum and thalamus were increased, whereas RGS9-2 and RGS11 mRNA were reduced in the cortex. Similar but attenuated RGS-R7 mRNA changes persisted 24h after acute morphine administration. No changes in Gbeta5 mRNA levels were observed. At 2 days after commencing sustained morphine treatment, the levels of mRNA for RGS7, RGS9-2, RGS11, and Gbeta5 increased in most of the brain structures studied (striatum, thalamus, periaqueductal gray matter (PAG), and cortex). In these morphine tolerant-dependent mice, the greater changes were found for RGS9-2 in the thalamus (> 500%) and PAG (> 200%). In post-dependent mice, the increases in RGS-R7 and Gbeta5 mRNA still persisted in the PAG and striatum at 8 and 16 days after starting the chronic opioid treatment. The raised mRNA levels promoted by chronic, but not by acute, morphine, were accompanied by increases in the encoded proteins. This is probably a result of the costabilization of the RGS-R7 and Gbeta5 proteins forming heterodimers. Opioid-induced adaptations of RGS-R7 and Gbeta5 genes may regulate the severity of morphine-induced tolerance/dependence and the duration of the post-dependent period, helping to recover the normal response. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 30 Issue Part 1 Page 99-110 Year of Publication 2005 Date of Publication Jan 2005 OPIOIDS (A) <515> Database EMBASE Accession Number 2005006533 Authors Stinus L. Cador M. Zorrilla E.P. Koob G.F. Institution (Stinus, Cador) Lab. Neuropsychobiol. Desadaptations, Universite de Bordeaux II, Bordeaux, Cedex, France. (Zorrilla, Koob) Department of Neuropharmacology, Scripps Research Institute, San Diego, CA, United States. (Stinus) Lab. Neuropsychobiol. Desadaptations, Universite de Bordeaux II, UMR-CNRS 5541, Bordeaux, Cedex 33076, France. Country of Publication United Kingdom Title Buprenorphine and a CRF<sub>1</sub> antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats. Source Neuropsychopharmacology. 30(1)(pp 90-98), 2005. Date of Publication: Jan 2005. Abstract Conditioned place aversion in rats has face validity as a measure of the aversive stimulus effects of opiate withdrawal that reflects an important motivational component of opiate dependence. The purpose of the present study was to validate conditioned place aversion as sensitive to medications that will alleviate the aversive stimulus effects of opiate withdrawal in humans, and to extend this model to the exploration of the neuropharmacological basis of the motivational effects of opiate withdrawal. Male Sprague-Dawley rats were implanted with two subcutaneous morphine pellets and 5 days later began place conditioning training following subcutaneous administration of a low dose of naloxone. Animals were subjected to three pairings of a low dose of naloxone (15 mug/kg, s.c.) to one arm of a three-chambered place conditioning apparatus, Buprenorphine administered prior to each pairing dose-dependently blocked the place aversion produced by precipitated opiate withdrawal, A corticotropinreleasing factor-1 (CRF<sub>1</sub>) receptor antagonist (antalarmin) also reversed the place aversion produced by precipitated opiate withdrawal. Antalarmin did not produce a place preference or place aversion by itself in morphine-dependent rats. No effect was observed with pretreatment of the dopamine partial agonist terguride or the selective serotonin reuptake inhibitor fluoxetine. Also, chronic pretreatment with acamprosate (a glutamate receptor modulator used to prevent relapse in alcohol dependence) did not alter naloxone-induced place aversion. Buprenorphine by itself in dependent rats produced a mild place preference at low doses and a mild place aversion at higher doses. These results suggest that buprenorphine blocks the aversive stimulus effects of precipitated opiate withdrawal in rats and provides some validity for the use of place conditioning as a measure that is sensitive to potential opiate-dependence medications. In addition, these results suggest that CRF<sub>1</sub> antagonists can block the aversive stimulus effects of opiate withdrawal and may be potential therapeutic targets for opiate dependence. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 30 Issue Part 1 Page 90-98 Year of Publication 2005 Date of Publication Jan 2005 OPIOIDS <522> Database EMBASE Accession Number 2004504633 Authors Feroni I. Peretti-Watel P. Masut A. Coudert C. Paraponaris A. Obadia Y. Institution (Feroni, Peretti-Watel, Paraponaris, Obadia) Inst. Natl. de la Rech. Med., U 379, 23 Rue Stanislas Torrents, 13006, Marseilles, France. (Masut, Coudert) Caisse Natl. d'Assur. Malad. B., 56 Chemin Joseph Aiguier, Marseilles, France. Country of Publication United Kingdom Title French general practitioners' prescribing high-dosage buprenorphine maintenance treatment: Is the existing training (good) enough? Source Addictive Behaviors. 30(1)(pp 187-191), 2005. Date of Publication: Jan 2005. Abstract In France, since 1996, any general practitioner (GP) can prescribe high-dosage buprenorphine maintenance treatment (BMT) for opioid-dependent patients. The health authorities initially provided mandatory specific training, but since 1998, such training is only delivered by specialized networks and the pharmaceutical industry. Among a random sample of GPs from southeastern France (N=345), we found that many untrained GPs, as well as a significant minority of trained GPs, were likely to prescribe an ineffective dosage of buprenorphine or a potentially dangerous treatment (BMT+a short half-life benzodiazepine). These results highlight the necessity to edit clear guidelines, especially concerning situations of polyaddiction and psychiatric comorbidity, and to extend and improve BMT training in France with a renewed involvement of health authorities for quality control of such training. They even suggest that GPs' participation to specialized training sessions should become a mandatory prerequisite for prescribing BMT. copyright 2004 Elsevier Ltd. All rights reserved. ISSN 0306-4603 Publication Type Journal: Article Journal Name Addictive Behaviors Volume 30 Issue Part 1 Page 187-191 Year of Publication 2005 Date of Publication Jan 2005 OPIOIDS (A) <525> Database EMBASE Accession Number 2004459697 Authors Grasing K. He S. Li N. Institution (Grasing, He, Li) Substance Abuse Research Laboratory, Kansas City Vet. Aff. Medical Center, 4801 Linwood Blvd., Kansas City, M., (Grasing) Division of Clinical Pharmacology, Department of Medicine, Univ. Kansas Sch. Med., Kansas C., Country of Publication United Kingdom Title Selegiline modifies the extinction of responding following morphine selfadministration, but does not alter cue-induced reinstatement, reacquisition of morphine reinforcement, or precipitated withdrawal. Source Pharmacological Research. 51(1)(pp 69-78), 2005. Date of Publication: Jan 2005. Abstract Selegiline is an irreversible inhibitor of monoamine oxidase (MAO) with psychostimulant and neuroprotective effects which can prevent decreases in dopamine efflux that follow opiate withdrawal. The present study evaluated effects of selegiline treatment on morphine-seeking behavior and morphine reinforcement in Wistar rats (n = 26). In additional animals (n = 30), the ability of single doses of selegiline to modify naloxone-precipitated withdrawal was determined. After pretreatment with noncontingent morphine to establish opiate dependence, rats acquired self-administration of intravenous morphine. Daily intravenous treatment with saline or 2.0 mg kg<sup>-1</sup> doses of selegiline was then initiated and continued over 14 days during extinction, reinstatement, and reacquisition of morphine self-administration. To reduce the potential for psychostimulant effects, selegiline was administered approximately 1 h following self-administration, extinction, or reinstatement sessions. In some animals (n = 23), effects of saline or selegiline administration on locomotor activity were determined following extinction sessions. Daily selegiline treatment decreased the number of ratios completed and increased response latency during extinction, without modifying these measures during reinstatement or reacquisition of morphine self-administration. Chronic selegiline treatment increased locomotor activity recorded between 4 and 7 h after selegiline administration on day 7 of extinction, but otherwise did not alter locomotor activity. Pretreatment with single, 2.0 mg kg<sup>-1</sup> doses of selegiline did not modify naloxone-precipitated withdrawal. In conclusion, pretreatment with selegiline produced only a small decrease in responding during extinction of morphine self-administration and did not modify cue-induced reinstatement of morphine-seeking behavior, reacquisition or morphine reinforcement, or precipitated withdrawal. copyright 2004 Elsevier Ltd. All rights reserved. ISSN 1043-6618 Publication Type Journal: Article Journal Name Pharmacological Research Volume 51 Issue Part 1 Page 69-78 Year of Publication 2005 Date of Publication Jan 2005 OPIOIDS <527> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 20407977 Status In-Process Authors Kreek MJ. Borg L. Ducat E. Ray B. Authors Full Name Kreek, Mary Jeanne. Borg, Lisa. Ducat, Elizabeth. Ray, Brenda. Institution Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA. kreek@rockefeller.edu Title Pharmacotherapy in the treatment of addiction: methadone. Source Journal of Addictive Diseases. 29(2):200-16, 2010 Apr. Journal Name Journal of Addictive Diseases Other ID Source: NLM. NIHMS179773 [Available on 04/01/11] Source: NLM. PMC2885886 [Available on 04/01/11] Country of Publication England Abstract Methadone maintenance treatment (MMT) is the most widely available pharmacotherapy for opioid addiction and has been shown to be an effective and safe treatment over a period of 40 years. Although women comprise approximately 40% of clients currently being treated in MMT programs, comparatively little research geared specifically toward this group has been published. This article begins with an overview of neurobiological studies on opioid addiction, including a discussion of gender differences, followed by a review of the pharmacology of methadone. The authors then examine the particular needs and differences of women being treated in MMTs, including co-dependence with other substances, women's health issues, and psychosocial needs unique to this population. Research shows that women have different substance abuse treatment needs in comparison to their male counterparts. One New York City MMT program that has attempted to address these differences is highlighted. Publication Type Journal Article. Research Support, N.I.H., Extramural. Research Support, Non-U.S. Gov't. Date of Publication 2010 Apr Year of Publication 2010 Issue/Part 2 Volume 29 Page 200-16 OPIOIDS <528> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 20535759 Status In-Process Authors Brownstein JS. Green TC. Cassidy TA. Butler SF. Authors Full Name Brownstein, John S. Green, Traci C. Cassidy, Theresa A. Butler, Stephen F. Institution Inflexxion Inc., Newton, MA 02464-1594, USA. Title Geographic information systems and pharmacoepidemiology: using spatial cluster detection to monitor local patterns of prescription opioid abuse. Source Pharmacoepidemiology & Drug Safety. 19(6):627-37, 2010 Jun. Journal Name Pharmacoepidemiology & Drug Safety Country of Publication England Abstract PURPOSE: Understanding the spatial distribution of opioid abuse at the local level may facilitate public health interventions. METHODS: Using patient-level data from addiction treatment facilities in New Mexico from ASI-MV Connect, we applied geographic information system (GIS) in combination with a spatial scan statistic to generate risk maps of prescription opioid abuse and identify clusters of product- and compound-specific abuse. Prescribed opioid volume data was used to determine whether identified clusters are beyond geographic differences in availability. RESULTS: Data on 24 452 patients residing in New Mexico were collected. Among those patients, 1779 (7.3%) reported abusing any prescription opioid (past 30 days). According to opioid type, 979 patients (4.0%) reported abuse of any hydrocodone, 1007 (4.1%) for any oxycodone, 108 (0.4%) for morphine, 507 (2.1%) for Vicodin or generic equivalent, 390 (1.6%) for OxyContin, and 63 (0.2%) for MS Contin or generic equivalent. Highest rates of abuse were found in the area surrounding Albuquerque with 8.6 patients indicating abuse per 100 interviewed patients. We found clustering of abuse around Albuquerque (P = 0.001; Relative Risk = 1.35, and a radius of 146 km). At the compound level, we found that drug availability was partly responsible for clustering of prescription opioid abuse. After accounting for drug availability, we identified a second foci of Vicodin abuse in the southern rural portion of the state near Las Cruces, NM and El Paso, Texas and bordering Mexico (RR = 2.1; P = 0.001). CONCLUSIONS: A better understanding of local risk distribution may have implications for response strategies to future introductions of prescription opioids. Publication Type Journal Article. Research Support, N.I.H., Extramural. Research Support, Non-U.S. Gov't. Date of Publication 2010 Jun Year of Publication 2010 Issue/Part 6 Volume 19 Page 627-37 OPIOIDS 2005 <633> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 16042795 Status PubMed-not-MEDLINE Authors Gerevich J. Bacskai E. Farkas L. Danics Z. Authors Full Name Gerevich, Jozsef. Bacskai, Erika. Farkas, Lajos. Danics, Zoltan. Institution Addiction Research Institute, Budapest. gerevichj@axelero.hu Title A case report: Pavlovian conditioning as a risk factor of heroin 'overdose' death. Source Harm Reduction Journal. 2:11, 2005 Jul 25. Journal Name Harm Reduction Journal Other ID Source: NLM. PMC1196296 Country of Publication England Abstract BACKGROUND: The authors present a case illustrating a mechanism leading directly to death which is not rare but has received little attention. CASE PRESENTATION: The case was evaluated by autopsy, investigation of morphine concentration in the blood, and clinical data. The heroin dose causing the 'overdose' death of a young man who had previously been treated a number of times for heroin addiction did not differ from his dose of the previous day taken in the accustomed circumstances. The accustomed dose taken in a strange environment caused fatal complications because the conditioned tolerance failed to operate. The concentration of morphine in the blood did not exceed the level measured during earlier treatment. CONCLUSION: These results are in line with the data in the literature indicating that morphine concentrations measured in cases of drug-related death do not differ substantially from those measured in cases where the outcome is not fatal. A knowledge of the conditioning mechanism can contribute to prevention of fatal cases of a similar type. The harm reduction approach places great stress on preventive intervention based on data related to drug-related death. Publication Type Journal Article. Date of Publication 2005 Jul 25 Year of Publication 2005 Volume 2 Page 11 OPIOIDS 2005 <944> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 16323564 Status MEDLINE Authors Frenois F. Le Moine C. Cador M. Authors Full Name Frenois, Francois. Le Moine, Catherine. Cador, Martine. Institution Interactions Neuronales et Comportements, Universite Victor Segalen, Bordeaux, France. ffrenois@bordeaux.inra.fr Title The motivational component of withdrawal in opiate addiction: role of associative learning and aversive memory in opiate addiction from a behavioral, anatomical and functional perspective. [Review] [154 refs] Source Reviews in the Neurosciences. 16(3):255-76, 2005. Journal Name Reviews in the Neurosciences Country of Publication England Abstract A major challenge in current drug addiction research is not only to understand the immediate effects of drugs of abuse on brain operations, but also to define at the behavioral and neural levels how cognitive, emotional and motivational processes interact with drug use in order to lead to this psychopathological state which defines addiction. It is now clear that factors other than the direct effects of drugs of abuse are able to powerfully affect drug-seeking and drugtaking behaviors. In former opiate addicts, re-exposure to environmental situations previously paired with withdrawal is able to induce strong craving episodes. It has been proposed that these conditioned stimuli could be strongly involved in precipitating relapse in drug-taking behavior by re-activating the neurobiological circuits which are engaged in an unconditioned way by the withdrawal state itself, leading to a powerful aversive state relieved by drug consumption renewal. In the present review, we provide evidence from a neuropsychopharmacological viewpoint that environmental situations previously paired with the opiate withdrawal syndrome might be able to maintain drug-seeking motivation. Using behavioral models which allow assessment of the aversive and motivational properties of opiate withdrawal both in the unconditioned and conditioned situations, we have recently investigated using extensive mapping the neurobiological correlates which underlie acute withdrawal and the trace of its memory in the brain in terms of localization and neuronal population involved, with an anatomical and functional approach. Thus, on the basis of our results, and together with a number of data in the literature, we provide a functional model for the formation and retrieval of opiate withdrawal memories. [References: 154] ISSN Print 0334-1763 Publication Type Journal Article. Research Support, Non-U.S. Gov't. Review. Date of Publication 2005 Year of Publication 2005 Issue/Part 3 Volume 16 Page 255-76 OPIOIDS 2005 <946> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 16262036 Status MEDLINE Authors Graham CH. Meechan JG. Authors Full Name Graham, Caroline H. Meechan, John G. Institution School of Dental Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, UK. Title Dental management of patients taking methadone. Source Dental Update. 32(8):477-8, 481-2, 485, 2005 Oct. Journal Name Dental Update Country of Publication England Abstract Methadone is a synthetic opiate used in the treatment of opiate addiction. Various sideeffects have been associated with the use of methadone. These include xerostomia, which can contribute to a high caries rate. The UK Regional Drug Misuse Database reported that around 118,500 drug users were receiving treatment from drug misuse agencies and GPs. The vast majority (87%) were receiving treatment from community specialist services. As many drug abusers have poor oral health, general dental practitioners are likely to encounter such individuals. It is essential therefore that dentists are aware of the potential difficulties that may be encountered when treating subjects receiving methadone. These problems may relate to previous drug abuse and to the effects of methadone therapy. ISSN Print 0305-5000 Publication Type Journal Article. Date of Publication 2005 Oct Year of Publication 2005 Issue/Part 8 Volume 32 Page 477-8, 481-2, 485 OPIOIDS (A) 2005 <964> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 16011579 Status MEDLINE Authors Szumlinski KK. Lominac KD. Frys KA. Middaugh LD. Authors Full Name Szumlinski, K K. Lominac, K D. Frys, K A. Middaugh, L D. Institution Department of Physiology and Neuroscience, and Department of Psychiatry and Behavioral Sciences, Center for Drug and Alcohol Programs, Medical University of South Carolina, Charleston, SC, USA. szumlink@musc.edu Title Genetic variation in heroin-induced changes in behaviour: effects of B6 strain dose on conditioned reward and locomotor sensitization in 129-B6 hybrid mice. Source Genes, Brain, & Behavior. 4(5):324-36, 2005 Jul. Journal Name Genes, Brain, & Behavior Country of Publication England Abstract Substantial interindividual variability exists in the propensity to develop opiate addiction. Genetic variation in opiate reward may contribute to this variability. A large body of evidence indicates genetic variation in mice for several effects of opiate drugs. The present study examined heroin-induced place conditioning and locomotor sensitization in the two strains of mice employed most frequently in the generation of transgenic animals, C57BL/6J (B6) and 129X1/sVJ (129), as well as in groups of B6-129 hybrid mice, differing in their amount of B6 genetic background. Four pairings of 100 microg/kg of heroin elicited robust place conditioning and locomotor sensitization in B6 controls and in N(10) congenic B6-129 hybrid mice. In comparison, the identical treatment produced no locomotor sensitization and induced place aversion in 129 controls. No heroin-induced changes in the behaviour of N(3) congenic B6-129 hybrid mice or F5-8 non-congenic B6-129 hybrid mice were observed. The expression of place conditioning was not facilitated in any group by the administration of a heroin-priming injection prior to testing. These data indicate that genetic variation exists in mice for the rewarding and locomotor-sensitizing effects of heroin and that the capacity of heroin to induce conditioned reward and locomotor sensitization can be modulated in a B6 strain dosedependent manner in B6-129 hybrid mice. Thus, strain differences in heroin responsiveness should be considered when examining transgenic lines on B6-129 backgrounds for opiateinduced changes in behaviour that may be relevant for addiction. ISSN Print 1601-1848 Publication Type Comparative Study. Journal Article. Research Support, N.I.H., Extramural. Research Support, Non-U.S. Gov't. Research Support, U.S. Gov't, P.H.S.. Date of Publication 2005 Jul Year of Publication 2005 Issue/Part 5 Volume 4 Page 324-36 OPIOIDS 2005 <983> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 15680308 Status MEDLINE Authors Sadee W. Wang D. Bilsky EJ. Authors Full Name Sadee, Wolfgang. Wang, Danxin. Bilsky, Edward J. Institution Department of Pharmacology, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, USA. sadee.1@osu.sdu Title Basal opioid receptor activity, neutral antagonists, and therapeutic opportunities. [Review] [61 refs] Source Life Sciences. 76(13):1427-37, 2005 Feb 11. Journal Name Life Sciences Country of Publication England Abstract The mu opioid receptor (MOR, OPRM)--the principal receptor involved in narcotic addiction-has been shown to display basal (spontaneous, constitutive) signaling activity. Interaction with other signaling proteins, such as calmodulin, regulates basal MOR activity. Providing a mechanism for long-lasting regulation, basal MOR activity potentially plays a key role in addiction, in combination with gene regulation and synaptic remodeling. Recent results support a link to physical dependence--one of the main manifestations of addiction to drugs of abuse. The prototypical opioid antagonists, naloxone and naltrexone, were shown to act as inverse agonists in the morphine-dependent state (i.e., they suppress basal MOR signaling) and thereby appear to elicit or contribute to precipitated withdrawal. This affords the opportunity to explore therapeutic applications for neutral antagonists (blocking agonists at MOR without affecting basal activity) with reduced adverse effects. Neutral antagonists are promising drug candidates in the treatment of addiction and overdose, and of peripheral adverse effects of narcotic analgesics. [References: 61] ISSN Print 0024-3205 Publication Type Journal Article. Research Support, U.S. Gov't, P.H.S.. Review. Date of Publication 2005 Feb 11 Year of Publication 2005 Issue/Part 13 Volume 76 Page 1427-37