NEURO 2009 <103>
Database EMBASE
Accession Number 0020175795
Authors Raffa R.B.
Institution (Raffa) Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA
19140, USA.
Country of Publication
United Kingdom
Title
The M5 muscarinic receptor as possible target for treatment of drug abuse.
Source
Journal of clinical pharmacy and therapeutics. 34(6)(pp 623-629), 2009. Date of Publication:
Dec 2009.
Abstract
Two reports published in the latter 1980s are generally given credit for being the first to
announce the discovery of a new subtype of muscarinic acetylcholine receptor (mAChR),
designated m5 or M5, and now officially M(5) (1). Both identifications were assigned using
molecular biology techniques. Then - as now - no selective high-affinity ligands or toxins were
available. In situ hybridization and reverse-transcriptase PCR have found M(5) AChR
expression in brain to be distinct from that of the four other G protein-coupled mAChR
subtypes and primarily localized to the substantia nigra, ventral tegmental area, hippocampus
(CA1 and CA2 subfields), cerebral cortex (outermost layer) and striatum (caudate putamen).
M(5) AChR brain region localization and involvement in the regulation of striatal dopamine
release and in rewarding brain stimulation suggests a possible role for M(5) AChR as a target
for novel therapy to treat excess hedonic drive, including drug abuse.
Publication Type Journal: Review
Journal Name Journal of clinical pharmacy and therapeutics
Volume 34
Issue Part 6
Page 623-629
Year of Publication 2009
Date of Publication Dec 2009
NEURO 2009 <162>
Database EMBASE
Accession Number 2008551146
Authors Chen A.L.-C. Chen T.J.H. Waite R.L. Reinking J. Tung H.L. Rhoades P. Downs B.W. Braverman E.
Braverman D. Kerner M. Blum S.H. DiNubile N. Smith D. Oscar-Berman M. Prihoda T.J. Floyd J.B. O'Brien D. Liu
H.H. Blum K.
Institution
(Chen, Chen) Chang Jung Christian University, Tainan, Taiwan (Republic of China).
(Chen) Changhua Christian Hospital, Changhua, Taiwan (Republic of China).
(Waite, Downs, Blum) LifeGen Inc., La Jolla, CA, United States.
(Reinking) Department of Rehabilitation Medicine, University of California, Davis Medical School, Davis, CA, United
States.
(Tung) Division of Neurological Surgery, University of California School of Medicine, La Jolla, CA, United States.
(Rhoades) Comprehensive Pain Clinic, Modesto, CA, United States.
(Braverman) Department of Neurological Surgery, Weill Cornell School of Medicine, New York, NY, United States.
(Braverman, Braverman, Kerner) Department of Research, PATH Research Foundation, New York, NY, United
States.
(Blum, Blum) Synaptamine Inc., San Antonio, TX, United States.
(DiNubile, Blum) Department of Orthopedic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA,
United States.
(Smith) Comprehensive Pain Management Clinic, San Diego, CA, United States.
(Oscar-Berman) Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston VA
Healthcare System, Boston, MA, United States.
(Prihoda) Department of Pathology, University of Texas Health Science Center, San Antonio, TX, United States.
(Floyd, O'Brien) Floyd, Skeren, and Kelly, PC, Los Angeles, CA, United States.
(Liu) Chung Shan Medical University, Taichung, Taiwan (Republic of China).
(Blum) Department Physiology and Pharmacology, Wake Forest University School of
Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, United States.
Country of Publication
United Kingdom
Title
Hypothesizing that brain reward circuitry genes are genetic antecedents of pain
sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic
pain conditions.
Source
Medical Hypotheses. 72(1)(pp 14-22), 2009. Date of Publication: January 2009.
Publisher
Churchill Livingstone
Abstract
While it is well established that the principal ascending pathways for pain originate in the
dorsal horn of the spinal cord and in the medulla, the control and sensitivity to pain may
reside in additional neurological loci, especially in the mesolimbic system of the brain (i.e., a
reward center), and a number of genes and associated polymorphisms may indeed impact
pain tolerance and or sensitivity. It is hypothesized that these polymorphisms associate with a
predisposition to intolerance or tolerance to pain. It is further hypothesized that identification
of certain gene polymorphisms provides a unique therapeutic target to assist in the treatment
of pain. It is hereby proposed that pharmacogenetic testing of certain candidate genes (i.e.,
mu receptors, PENK etc.) will result in pharmacogenomic solutions personalized to the
individual patient, with potential improvement in clinical outcomes. copyright 2008 Elsevier
Ltd. All rights reserved.
ISSN 0306-9877
Publication Type Journal: Article
Journal Name Medical Hypotheses
Volume 72
Issue Part 1
Page 14-22
Year of Publication 2009
Date of Publication January 2009
NEURO 2009 <587>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 20003358
Status In-Data-Review
Authors Al-Zahrani MA. Elsayed YA.
Authors Full Name Al-Zahrani, Mohamed A. Elsayed, Yasser A.
Institution
Al-Amal Complex for Mental Health, PO 5054, Dammam 31422, Saudia Arabia. yarazek68@gmail.com.
Title
The impacts of substance abuse and dependence on neuropsychological functions in
a sample of patients from Saudi Arabia.
Source
Behavioral & Brain Functions [Electronic Resource]: BBF. 5:48, 2009.
Journal Name
Behavioral & Brain Functions [Electronic Resource]: BBF
Other ID
Source: NLM. PMC2799426
Country of Publication
England
Abstract
ABSTRACT: BACKGROUND: A lot of studies were directed to explore the relation between
drug abuse and neuropsychological functions. Some studies reported that even after a long
duration of disappearance of withdrawal or intoxication symptoms, many patients have
obvious deterioration of cognitive functions. The aim of this study was to explore the
relationship between the substance use disorders and the executive functions. METHODS:
Two groups were selected for this study. An experimental group consisted of 154 patients and
further subdivided according to the substance used into three different subgroups: opioid,
amphetamine and alcohol groups which included 49, 56 and 49 patients respectively. The
control group was selected matching the experimental group in the demographic
characteristics and included 100 healthy persons. Tools used were: Benton visual retention
tests, color trail making test, Stroop colors-word test, symbol digit modalities test, the five dots
cognitive flexibility test, and TAM verbal flexibility test. All the data were subjected to statistical
analysis RESULTS: The study showed that the group of drug-dependent subjects performed
significantly worse than the comparison group on all measures Also, there were significant
differences among the subgroups as the alcoholic group was much worse followed by the
amphetamine then the opioids groups. Patients with longer duration of dependence and
multiple hospital readmissions were much worse in comparison to patients with shorter
duration of dependence and less readmission. CONCLUSION: The study confirmed that the
functions of specific brain regions underlying cognitive control are significantly impaired in
patients of drug addiction. This impairment was significantly related to type of substance,
duration of use and number of hospitalization and may contribute to most of behavioral
disturbances found in addicts and need much attention during tailoring of treatment programs.
Publication Type Journal Article.
Date of Publication 2009
Year of Publication 2009
Volume 5
Page 48
NEURO 2009 <601>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 19419578
Status In-Data-Review
Authors Zhang H. Li S. Wang M. Vukusic B. Pristupa ZB. Liu F.
Authors Full Name Zhang, Heping. Li, Shupeng. Wang, Min. Vukusic, Brian. Pristupa, Zdenek B. Liu, Fang.
Institution
Department of Neuroscience, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
fang_liu@camh.net.
Title
Regulation of dopamine transporter activity by carboxypeptidase E.
Source
Molecular Brain. 2(1):10, 2009.
Journal Name
Molecular Brain
Other ID
Source: NLM. PMC2687442
Country of Publication
England
Abstract
ABSTRACT: BACKGROUND: The dopamine transporter (DAT) plays a critical role in
terminating the action of dopamine by rapid reuptake into the presynaptic neuron. Previous
studies have revealed that the DAT carboxyl terminus (DAT-CT) can directly interact with
other cellular proteins and regulate DAT function and trafficking. RESULTS: Here, we have
identified that carboxypeptidase E (CPE), a prohormone processing exopeptidase and sorting
receptor for the regulated secretory pathway, interacts with the DAT-CT and affects DAT
function. Mammalian cell lines coexpressing CPE and DAT exhibited increased DATmediated dopamine uptake activity compared to cells expressing DAT alone. Moreover,
coexpression of an interfering DAT-CT minigene inhibited the effects of CPE on DAT.
Functional changes caused by CPE could be attributed to enhanced DAT expression and
subsequent increase in DAT cell surface localization, due to decreased DAT degradation. In
addition, CPE association could reduce the phosphorylation state of DAT on serine residues,
potentially leading to reduced internalization, thus stabilizing plasmalemmal DAT localization.
CONCLUSION: Taken together, our results reveal a novel role for CPE in the regulation of
DAT trafficking and DAT-mediated DA uptake, which may provide a novel target in the
treatment of dopamine-governed diseases such as drug addiction and obesity.
Publication Type Journal Article.
Date of Publication 2009
Year of Publication 2009
Issue/Part 1
Volume 2
Page 10
NEURO (A) 2009 <653>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 19393282
Status MEDLINE
Authors O'Mara SM. Sanchez-Vives MV. Brotons-Mas JR. O'Hare E.
Authors Full Name O'Mara, Shane M. Sanchez-Vives, Maria V. Brotons-Mas, Jorge R. O'Hare, Eugene.
Institution
Trinity College Institute of Neuroscience and School of Psychology, Trinity College-University of Dublin, Dublin 2,
Ireland.
Title
Roles for the subiculum in spatial information processing, memory, motivation and
the temporal control of behaviour. [Review] [68 refs]
Source
Progress in Neuro-Psychopharmacology & Biological Psychiatry. 33(5):782-90, 2009 Aug 1.
Journal Name
Progress in Neuro-Psychopharmacology & Biological Psychiatry
Country of Publication
England
Abstract
The subiculum is in a pivotal position governing the output of the hippocampal formation.
Despite this, it is a rather under-explored and sometimes ignored structure. Here, we discuss
recent data indicating that the subiculum participates in a wide range of neurocognitive
functions and processes. Some of the functions of subiculum are relatively well-known-these
include providing a relatively coarse representation of space and participating in, and
supporting certain aspects of, memory (particularly in the dynamic bridging of temporal
intervals). The subiculum also participates in a wide variety of other neurocognitive functions
too, however. Much less well-known are roles for the subiculum, and particularly the ventral
subiculum, in the response to fear, stress and anxiety, and in the generation of motivated
behaviour (particularly the behaviour that underlies drug addiction and the response to
reward). There is an emerging suggestion that the subiculum participates in the temporal
control of behaviour. It is notable that these latter findings have emerged from a consideration
of instrumental behaviour using operant techniques; it may well be the case that the use of
the watermaze or similar spatial tasks to assess subicular function (on the presumption that
its functions are very similar to the hippocampus proper) has obscured rather than revealed
neurocognitive functions of subiculum. The anatomy of subiculum suggests it participates in a
rather subtle fashion in a very broad range of functions, rather than in a relatively more
isolated fashion in a narrower range of functions, as might be the case for "earlier"
components of hippocampal circuitry, such as the CA1 and CA3 subfields. Overall, there
appears to a strong dorso-ventral segregation of function within subiculum, with the dorsal
subiculum relatively more concerned with space and memory, and the ventral hippocampus
concerned with stress, anxiety and reward. Finally, it may be the case that the whole
subiculum participates in the temporal control of reinforced behaviour, although further
experimentation is required to clarify this hypothesis. [References: 68]
Publication Type Journal Article. Research Support, Non-U.S. Gov't. Review.
Date of Publication 2009 Aug 1
Year of Publication 2009
Issue/Part 5
Volume 33
Page 782-90
NEURO (A) <666>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 19616054
Status MEDLINE
Authors Jalabert M. Aston-Jones G. Herzog E. Manzoni O. Georges F.
Authors Full Name Jalabert, Marion. Aston-Jones, Gary. Herzog, Etienne. Manzoni, Olivier. Georges, Francois.
Institution
INSERM, U862, Neurocentre Magendie, Pathophysiology of synaptic plasticity group,
Bordeaux, F-33000, France.
Title
Role of the bed nucleus of the stria terminalis in the control of ventral tegmental area
dopamine neurons.
Source
Progress in Neuro-Psychopharmacology & Biological Psychiatry. 33(8):1336-46, 2009 Nov
13.
Journal Name
Progress in Neuro-Psychopharmacology & Biological Psychiatry
Country of Publication
England
Abstract
Projections from neurons of the bed nucleus of the stria terminalis (BST) to the ventral
tegmental area (VTA) are crucial to behaviors related to reward and motivation. Over the past
few years, we have undertaken a series of studies to understand: 1) how excitatory inputs
regulate in vivo excitable properties of BST neurons, and 2) how BST inputs in turn modulate
neuronal activity of dopamine neurons in VTA. Using in vivo extracellular recording
techniques in anesthetized rats and tract-tracing approaches, we have demonstrated that
inputs from the infralimbic cortex and the ventral subiculum exert a strong excitatory influence
on BST neurons projecting to the VTA. Thus, the BST is uniquely positioned to receive
emotional and learning-associated informations and to integrate these into the
reward/motivation circuitry. We will discuss how changes in the activity of BST neurons
projecting to the VTA could participate in the development or exacerbation of psychiatric
conditions such as drug addiction.
Publication Type Journal Article. Research Support, Non-U.S. Gov't.
Date of Publication 2009 Nov 13
Year of Publication 2009
Issue/Part 8
Volume 33
Page 1336-46
NEURO (A) <667>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 19524008
Status MEDLINE
Authors McElligott ZA. Winder DG.
Authors Full Name McElligott, Zoe Anastasia. Winder, Danny G.
Institution
Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Title
Modulation of glutamatergic synaptic transmission in the bed nucleus of the stria
terminalis. [Review] [120 refs]
Source
Progress in Neuro-Psychopharmacology & Biological Psychiatry. 33(8):1329-35, 2009 Nov
13.
Journal Name
Progress in Neuro-Psychopharmacology & Biological Psychiatry
Other ID
Source: NLM. NIHMS123689 [Available on 11/13/10]
Source: NLM. PMC2783684 [Available on 11/13/10]
Country of Publication
England
Abstract
Glutamate, catecholamine and neuropeptide signaling within the bed nucleus of the stria
terminalis (BNST) have all been identified as key participants in anxiety-like behaviors and
behaviors related to withdrawal from exposure to substances of abuse. The BNST is thought
to serve as a key relay between limbic cognitive centers and reward, stress and anxiety
nuclei. Human studies and animal models have demonstrated that stressors and drugs of
abuse can result in long term behavioral modifications that can culminate in psychological
diseases such as addiction and post-traumatic stress disorder. The ability of catecholamines
and neuropeptides to influence synaptic glutamatergic transmission (stemming from cognitive
centers) within the BNST may have profound consequences over these behaviors. In this
review we highlight studies examining synaptic plasticity and modulation of excitatory
transmission within the BNST, emphasizing how such modulation may result in alterations in
anxiety and reward related behavior. [References: 120]
Publication Type Journal Article. Review.
Date of Publication 2009 Nov 13
Year of Publication 2009
Issue/Part 8
Volume 33
Page 1329-35
NEURO (A) <671>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 19615345
Status MEDLINE
Authors Ji J. Bourque M. Di Paolo T. Dluzen DE.
Authors Full Name
Ji, Jing. Bourque, Melanie. Di Paolo, Therese. Dluzen, Dean E.
Institution
Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown, OH 44272, USA.
Title
Genetic alteration in the dopamine transporter differentially affects male and female
nigrostriatal transporter systems.
Source
Biochemical Pharmacology. 78(11):1401-11, 2009 Dec 1.
Journal Name
Biochemical Pharmacology
Country of Publication
England
Abstract
Female mice with a heterozygous mutation of their dopamine transporter (+/- DAT) showed
relatively robust reductions in striatal DAT specific binding (38-50%), while +/- DAT males
showed modest reductions (24-32%). Significant decreases in substantia nigra DAT specific
binding (42%) and mRNA (24%) were obtained in +/- DAT females, but not +/- DAT males
(19% and 5%, respectively). The effects of this DAT perturbation upon vesicular monoamine
transporter-2 (VMAT-2) function revealed significantly greater reserpine-evoked DA output
from +/+ and +/- DAT female as compared to male mice and the DA output profile differed
markedly between +/+ and +/- DAT females, but not males. No changes in VMAT-2 protein or
mRNA levels were present among these conditions. On the basis of these data, we propose:
(1) a genetic mutation of the DAT does not exert equivalent effects upon the DAT in female
and male mice, with females being more affected; (2) an alteration in the DAT may also affect
VMAT-2 function; (3) this interaction between DAT and VMAT-2 function is more prevalent in
female mice; and (4) the +/- DAT mutation affects VMAT-2 function through an indirect
mechanism, that does not involve an alteration in VMAT-2 protein or mRNA. Such
DAT/VMAT-2 interactions can be of significance to the gender differences observed in drug
addiction and Parkinson's disease.
Publication Type Comparative Study. Journal Article. Research Support, Non-U.S. Gov't.
Date of Publication 2009 Dec 1
Year of Publication 2009
Issue/Part 11
Volume 78
Page 1401-11
NEURO (GENETICS) <702>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 19208180
Status MEDLINE
Authors Long Q. Zhang Q. Ott J.
Authors Full Name Long, Quan. Zhang, Qingrun. Ott, Jurg.
Institution
Beijing Institute of Genomics, Chinese Academy of Sciences, No, 7 Bei Tu Cheng West Road, Beijing 100029, PR
China. ql2@sanger.ac.uk
Title
Detecting disease-associated genotype patterns.
Source
BMC Bioinformatics. 10 Suppl 1:S75, 2009.
Journal Name
BMC Bioinformatics
Other ID
Source: NLM. PMC2648768
Country of Publication
England
Abstract
BACKGROUND: In addition to single-locus (main) effects of disease variants, there is a
growing consensus that gene-gene and gene-environment interactions may play important
roles in disease etiology. However, for the very large numbers of genetic markers currently in
use, it has proven difficult to develop suitable and efficient approaches for detecting effects
other than main effects due to single variants. RESULTS: We developed a method for jointly
detecting disease-causing single-locus effects and gene-gene interactions. Our method is
based on finding differences of genotype pattern frequencies between case and control
individuals. Those single-nucleotide polymorphism markers with largest single-locus
association test statistics are included in a pattern. For a logistic regression model comprising
three disease variants exerting main and epistatic interaction effects, we demonstrate that our
method is vastly superior to the traditional approach of looking for single-locus effects. In
addition, our method is suitable for estimating the number of disease variants in a dataset.
We successfully apply our approach to data on Parkinson Disease and heroin addiction.
CONCLUSION: Our approach is suitable and powerful for detecting disease susceptibility
variants with potentially small main effects and strong interaction effects. It can be applied to
large numbers of genetic markers.
Publication Type Journal Article. Research Support, N.I.H., Extramural. Research Support, Non-U.S. Gov't.
Date of Publication 2009
Year of Publication 2009
Volume 10 Suppl 1
Page S75
NEURO 2009 <704>
Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
Unique Identifier 19174218
Status MEDLINE
Authors Mercolini L. Gerra G. Consorti M. Somaini L. Raggi MA.
Authors Full Name Mercolini, Laura. Gerra, Gilberto. Consorti, Marco. Somaini, Lorenzo. Raggi, Maria Augusta.
Institution
Faculty of Pharmacy, Department of Pharmaceutical Sciences, Alma Mater Studiorum-University of Bologna,
Bologna, Italy.
Title
Fast analysis of catecholamine metabolites MHPG and VMA in human plasma by
HPLC with fluorescence detection and a novel SPE procedure.
Source
Talanta. 78(1):150-5, 2009 Apr 15.
Journal Name
Talanta
Country of Publication
England
Abstract
A fast and sensitive high-performance liquid chromatographic method has been developed
for the determination in human plasma of MHPG (3-methoxy-4-hydroxyphenylethylenglycol)
and VMA (vanillyl mandelic acid), the main metabolites of epinephrine and norepinephrine.
Analyses were carried out at 325 nm while exciting at 285 nm on a reversed-phase column
(Atlantis C18, 150 mm x 4.6 mm I.D., 5 microm) using a mobile phase composed of 2%
methanol and 98% aqueous citrate buffer at pH 3.0. A careful solid-phase extraction
procedure, based on mixed-mode reversed-phase - strong anion exchange Oasis cartridges
(MAX, 30 mg, 1 mL), was developed for the pre-treatment of plasma samples. Extraction
yields were satisfactory, always higher than 90%. Calibration curves were linear over the 0.240.0 ng mL(-1) concentration range for MHPG and over the 0.5-40.0 ng mL(-1) concentration
range for VMA. The method was successfully applied to plasma samples of former drug users
undergoing detoxification therapy and subjects "at risk" of developing drug addiction.
Publication Type Journal Article. Research Support, Non-U.S. Gov't.
Date of Publication 2009 Apr 15
Year of Publication 2009
Issue/Part 1
Volume 78
Page 150-5
NEURO 2009 <142>
Database EMBASE
Accession Number 2009108380
Authors Weitemier A.Z. Murphy N.P.
Institution
(Weitemier, Murphy) Molecular Neuropathology Research Group, RIKEN Brain Science Institute, 2-1 Hirosawa,
Wakoshi, Saitama 351-0198, Japan.
Country of Publication
United Kingdom
Title
Accumbal dopamine and serotonin activity throughout acquisition and expression of
place conditioning: Correlative relationships with preference and aversion.
Source
European Journal of Neuroscience. 29(5)(pp 1015-1026), 2009. Date of Publication: March
2009.
Publisher
Blackwell Publishing Ltd
Abstract
The ability of addictive drugs to induce adaptations in mesolimbic dopamine (DA) activity
offers an attractive neurobiological explanation for enhanced incentive motivation toward
drug-associated stimuli in addiction. However, direct evidence supporting this is sparse. By
tracking neurochemical activity within the mouse nucleus accumbens via microdialysis during
repeated pairing of morphine with environmental stimuli, we reveal a predictive relationship
between enhanced DA responses to morphine and subsequent preference towards a
morphine-paired stimulus. A similar relationship for serotonin (5-HT) was observed,
suggesting that these neuromodulatory systems work in concert. During expression of
preference towards a morphine-paired stimulus, extracellular DA was not enhanced but was
negatively associated with this behavior on a subject-by-subject basis. In contrast, avoidance
of an aversively-paired stimulus (the opiate antagonist naloxone) was associated with
enhanced extracellular DA levels, and also the balance between DA and 5-HT responses.
These findings reveal a tangible predictive relationship between drug-induced neural
adaptations and conditioned behavior, and emphasize that DA activity is not generalized to all
subcomponents of behavior conditioned by addictive drugs. They further provide evidence for
an active role of DA-5-HT interactions in the expression of learned behavior. copyright
Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
ISSN 0953-816X
Publication Type Journal: Article
Journal Name European Journal of Neuroscience
Volume 29
Issue Part 5
Page 1015-1026
Year of Publication 2009
Date of Publication March 2009
NEURO 2009 <145>
Database EMBASE
Accession Number 2009101570
Authors Traynor J.R. Terzi D. Caldarone B.J. Zachariou V.
Institution
(Traynor) Department of Pharmacology, Substance Abuse Research Center, University of Michigan, Ann Arbor, MI
48109, United States.
(Terzi, Zachariou) Department of Pharmacology, University of Crete Faculty of Medicine, Heraklion, 71003 Crete,
Greece.
(Caldarone) PsychoGenics, 765 Old Saw Mill River, Road, Tarrytown, NY 10591, United States.
Country of Publication
United Kingdom
Title
RGS9-2: probing an intracellular modulator of behavior as a drug target.
Source
Trends in Pharmacological Sciences. 30(3)(pp 105-111), 2009. Date of Publication: March
2009.
Publisher
Elsevier Ltd
Abstract
Regulators of G-protein signaling (RGS proteins) comprise a large family of signal
transduction molecules that modulate G-protein-coupled-receptor (GPCR) function. Among
the RGS proteins expressed in the brain, RGS9-2 is very abundant in the striatum, a brain
region involved in movement, motivation, mood and addiction. This protein negatively
modulates signal transduction thus playing a key part in striatal function and resultant
behavioral responses. In particular, there is evidence of important interactions with mu-opioidand dopamine D2-receptor signaling pathways. Several studies indicate that manipulations of
RGS9-2 levels in the striatum might greatly affect pharmacological responses. These findings
indicate that treatment strategies targeting RGS9-2 levels or activity might be used to
enhance responses to drugs acting at GPCRs and/or prevent undesired drug actions.
copyright 2008 Elsevier Ltd. All rights reserved.
ISSN 0165-6147
Publication Type Journal: Article
Journal Name Trends in Pharmacological Sciences
Volume 30
Issue Part 3
Page 105-111
Year of Publication 2009
Date of Publication March 2009
NEURO 2009 <146>
Database EMBASE
Accession Number 2009098514
Authors Brami-Cherrier K. Roze E. Girault J.-A. Betuing S. Caboche J.
Institution
(Brami-Cherrier, Roze, Betuing, Caboche) UMRS 952, INSERM, Universite Pierre et Marie Curie-Paris-6, Paris,
France.
(Brami-Cherrier, Girault) UMR-S 839, Inserm, Institut du Fer A Moulin, Paris, France.
(Roze) Pole des Maladies du Systeme Nerveux, Federation de Neurologie, AP-HP, Paris, France.
(Betuing) Universite d'Evry Val d'Essonne, Boulevard Francois Mitterand, Evry, Cedex, France.
(Caboche) UMRS 952, INSERM, Universite Pierre et Marie Curie-Paris-6, 9 quai Saint Bernard, 75005 Paris,
France.
Country of Publication
United Kingdom
Title
Role of the ERK/MSK1 signalling pathway in chromatin remodelling and brain
responses to drugs of abuse.
Source
Journal of Neurochemistry. 108(6)(pp 1323-1335), 2009. Date of Publication: March 2009.
Publisher
Blackwell Publishing Ltd
Abstract
Drugs of abuse induce neuroadaptations through regulation of gene expression. Although
much attention has focused on transcription factor activities, new concepts have recently
emerged on the role of chromatin remodelling as a prerequisite for regulation of gene
expression in neurons. Thus, for transcription to occur, chromatin must be decondensed, a
dynamic process that depends on post-translational modifications of histones. We review
here these modifications with a particular emphasis on the role of histone H3 phosphorylation
at the promoter of specific genes, including c-fos and c-jun. We trace the signalling pathways
involved in H3 phosphorylation and provide evidence for a role of mitogen and stressactivated protein kinase-1 (MSK1) downstream from the MAPK/extracellular-signal regulated
kinase (ERK) cascade. In response to cocaine, MSK1 controls an early phase of histone H3
phosphorylation at the c-fos promoter in striatal neurons. MSK1 action may be potentiated by
the concomitant inhibition of protein phosphatase 1 by nuclear translocation of dopamine- and
cAMP-regulated phosphoprotein Mr = 32 000. H3 phosphorylation by MSK1 is critically
involved in c-fos transcription, and cocaine-induced locomotor sensitization. Thus, ERK plays
a dual role in gene regulation and drug addiction by direct activation of transcription factors
and by chromatin remodelling. copyright 2009 International Society for Neurochemistry.
ISSN 0022-3042
Publication Type Journal: Review
Journal Name Journal of Neurochemistry
Volume 108
Issue Part 6
Page 1323-1335
Year of Publication 2009
Date of Publication March 2009
NEURO 2009 <161>
Database EMBASE
Accession Number 2009086563
Authors Buydens-Branchey L. Branchey M. Hibbeln J.R.
Institution
(Buydens-Branchey) Psychiatry Service, DVA New York Harbor Healthcare System, Brooklyn, NY, United States.
(Branchey, Hibbeln) National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, United States.
(Buydens-Branchey) Narrows Institute for Biomedical Research, 800 Poly Place, Brooklyn, NY 11209, United
States.
Country of Publication
United Kingdom
Title
Low plasma levels of docosahexaenoic acid are associated with an increased relapse
vulnerability in substance abusers.
Source
American Journal on Addictions. 18(1)(pp 73-80), 2009. Date of Publication: January 2009.
Publisher
Informa Healthcare
Abstract
Low levels of some polyunsaturated fatty acids (PUFAs) could influence behaviors leading to
the abuse of substances through their actions on serotonergic and dopaminergic
mechanisms. Because substance abusers tend to have poor dietary habits, the possibility that
a deficient intake of n-3 PUFAs, available from dietary sources only, and subsequent low n-3
plasma levels would predict their relapse rates was explored. Thirty-five patients admitted to
substance abuse clinics were enrolled and followed for one year. Dietary questionnaires and
blood samples were collected at baseline and on a quarterly basis, and relapse rates
monitored on a monthly basis. Six patients dropped out shortly after study entry, 11 relapsed
in the course of the study and dropped out, 7 relapsed but completed the study, and 11 did
not relapse and completed the study. Non-relapsers were found to have significantly higher
levels of docosahexaenoic acid (DHA) calculated as mug/ml and % TFA, when compared to
relapsers (p =.031 and p =.010, respectively) and to relapsers and non-completers combined
(p =.014 and p =.009, respectively). These pilot data suggest, but do not prove, the existence
of a relationship between low levels of DHA and relapse vulnerability in some individuals who
abuse substances. The study of the efficacy of n-3 supplements or of dietary modifications on
relapse appears warranted. Copyright copyright American Academy of Addiction Psychiatry.
ISSN 1055-0496
Publication Type Journal: Article
Journal Name American Journal on Addictions
Volume 18
Issue Part 1
Page 73-80
Year of Publication 2009
Date of Publication January 2009
NEURO 2009 <178>
Database EMBASE
Accession Number 2009057502
Authors Carter M.E. Borg J.S. de Lecea L.
Institution
(Carter, Borg, de Lecea) Department of Psychiatry and Behavioral Sciences, Stanford University, 701B Welch
Road, Palo Alto, CA 94304, United States.
Country of Publication
United Kingdom
Title
The brain hypocretins and their receptors: mediators of allostatic arousal.
Source
Current Opinion in Pharmacology. 9(1)(pp 39-45), 2009. Date of Publication: February
2009.
Publisher
Elsevier Ltd
Abstract
The hypocretins (abbreviated 'Hcrts' - also called 'orexins') are two neuropeptides secreted
exclusively by a small population of neurons in the lateral hypothalamus. These peptides bind
to two receptors located throughout the brain in nuclei associated with diverse cognitive and
physiological functions. Initially, the brain Hcrt system was found to have a major role in the
regulation of sleep/wake transitions. More recent studies indicate Hcrts may play a role in
other physiological functions, including food intake, addiction, and stress. Taken together,
these studies suggest a general role for Hcrts in mediating arousal, especially when an
organism must respond to unexpected stressors and challenges in the environment. copyright
2009.
ISSN 1471-4892
Publication Type Journal: Review
Journal Name Current Opinion in Pharmacology
Volume 9
Issue Part 1
Page 39-45
Year of Publication 2009
Date of Publication February 2009
NEURO 2009 <181>
Database EMBASE
Accession Number 2009057501
Authors Kreek M.J. Zhou Y. Butelman E.R. Levran O.
Institution
(Kreek, Zhou, Butelman, Levran) The Rockefeller University, Laboratory of the Biology of Addictive Diseases, 1230
York Avenue, New York, NY 10065, United States.
Country of Publication
United Kingdom
Title
Opiate and cocaine addiction: from bench to clinic and back to the bench.
Source
Current Opinion in Pharmacology. 9(1)(pp 74-80), 2009. Date of Publication: February
2009.
Publisher
Elsevier Ltd
Abstract
This review primarily focuses on our recent findings in bidirectional translational research on
opiate and cocaine addictions. First, we present neurobiological and molecular studies on
endogenous opioid systems (e.g. proopiomelanocortin, mu opioid receptor, dynorphin, and
kappa opioid receptor), brain stress-responsive systems (e.g. orexin, arginine vasopressin,
V1b receptor, and corticotropin-releasing factor), hypothalamic-pituitary-adrenal axis, and
neurotransmitters (especially dopamine), in response to both chronic cocaine or opiate
exposure and to drug withdrawal, using several newly developed animal models and
molecular approaches. The second aspect is human molecular genetic association
investigations including hypothesis-driven studies and genome-wide array studies, to define
particular systems involved in vulnerability to develop specific addictions, and response to
pharmacotherapy. copyright 2009.
ISSN 1471-4892
Publication Type Journal: Review
Journal Name Current Opinion in Pharmacology
Volume 9
Issue Part 1
Page 74-80
Year of Publication 2009
Date of Publication February 2009
NEURO 2009 <182>
Database EMBASE
Accession Number 2009057493
Authors De Mei C. Ramos M. Iitaka C. Borrelli E.
Institution
(De Mei, Ramos, Iitaka, Borrelli) University of California Irvine, Department of Microbiology and Molecular Genetics,
3113 Gillespie NRF, Irvine, CA 92617, United States.
Country of Publication
United Kingdom
Title
Getting specialized: presynaptic and postsynaptic dopamine D2 receptors.
Source
Current Opinion in Pharmacology. 9(1)(pp 53-58), 2009. Date of Publication: February
2009.
Publisher
Elsevier Ltd
Abstract
Dopamine (DA) signaling controls many physiological functions ranging from locomotion to
hormone secretion, and plays a critical role in addiction. DA elevation, for instance in
response to drugs of abuse, simultaneously activates neurons expressing different DA
receptors; how responses from diverse neurons/receptors are orchestrated in the generation
of behavioral and cellular outcomes, is still not completely defined. Signaling from D2
receptors (D2Rs) is a good example to illustrate this complexity. D2Rs have presynaptic and
postsynaptic localization and functions, which are shared by two isoforms in vivo. Recent
results from knockout mice are clarifying the role of site and D2 isoform-specific effects
thereby increasing our understanding of how DA modulates neuronal physiology. copyright
2008 Elsevier Ltd. All rights reserved.
ISSN 1471-4892
Publication Type Journal: Review
Journal Name Current Opinion in Pharmacology
Volume 9
Issue Part 1
Page 53-58
Year of Publication 2009
Date of Publication February 2009
NEURO 2009 <184>
Database EMBASE
Accession Number 2009000502
Authors Stella N.
Institution
(Stella) Department of Pharmacology, Psychiatry and Behavioral Sciences, University of Washington, 1959 NE
Pacific Street, Seattle, WA 98195-7280, United States.
Country of Publication
United Kingdom
Title
Endocannabinoid signaling in microglial cells.
Source
Neuropharmacology. 56(SUPPL. 1)(pp 244-253), 2009. Date of Publication: 2009.
Publisher
Elsevier Ltd
Abstract
The endocannabinoid signaling system (eCBSS) is composed of cannabinoid (CB)
receptors, their endogenous ligands (the endocannabinoids, eCB) and the enzymes that
produce and inactivate these ligands. Neurons use this signaling system to communicate with
each other and Delta9-tetrahydrocannabinol (THC), the main psychotropic ingredient of
Cannabis sativa, induces profound behavioral effects by impinging on this communication.
Evidence now shows that microglia, the macrophages of the brain, also express a functional
eCBSS and that activation of CB receptors expressed by activated microglia controls their
immune-related functions. This review summarizes this evidence, discusses how microglia
might use the eCBSS to communicate with each other and neighboring cells, and argues that
compounds selectively targeting the eCBSS expressed by microglia constitute valuable
therapeutics to manage acute and chronic neuroinflammation, without inducing the
psychotropic effects and underlying addictive properties commonly associated with THC.
ISSN 0028-3908
Publication Type Journal: Review
Journal Name Neuropharmacology
Volume 56
Issue Part SUPPL. 1
Page 244-253
Yearof Publication 2009
Date of Publication 2009
NEURO 2009 <187>
Database EMBASE
Accession Number 2009000504
Authors Koob G.F.
Institution
(Koob) Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey
Pines Road, SP30-2400, La Jolla, CA 92037, United States.
Country of Publication
United Kingdom
Title
Neurobiological substrates for the dark side of compulsivity in addiction.
Source
Neuropharmacology. 56(SUPPL. 1)(pp 18-31), 2009. Date of Publication: 2009.
Publisher
Elsevier Ltd
Abstract
Drug addiction can be defined by a compulsion to seek and take drug, loss of control in
limiting intake, and the emergence of a negative emotional state when access to the drug is
prevented. Drug addiction impacts multiple motivational mechanisms and can be
conceptualized as a disorder that progresses from impulsivity (positive reinforcement) to
compulsivity (negative reinforcement). The construct of negative reinforcement is defined as
drug taking that alleviates a negative emotional state. The negative emotional state that
drives such negative reinforcement is hypothesized to derive from dysregulation of key
neurochemical elements involved in reward and stress within the basal forebrain structures
involving the ventral striatum and extended amygdala. Specific neurochemical elements in
these structures include not only decreases in reward neurotransmission, such as decreases
in dopamine and opioid peptide function in the ventral striatum, but also recruitment of brain
stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala.
Acute withdrawal from all major drugs of abuse produces increases in reward thresholds,
increases in anxiety-like responses, and increases in extracellular levels of CRF in the central
nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake
produced by dependence. A brain stress response system is hypothesized to be activated by
acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into
protracted abstinence, and to contribute to the compulsivity of addiction. Other components of
brain stress systems in the extended amygdala that interact with CRF and may contribute to
the negative motivational state of withdrawal include norepinephrine, dynorphin, and
neuropeptide Y. The combination of loss of reward function and recruitment of brain stress
systems provides a powerful neurochemical basis for a negative emotional state that is
responsible for the negative reinforcement driving, at least in part, the compulsivity of
addiction. copyright 2008 Elsevier Ltd. All rights reserved.
ISSN 0028-3908
Publication Type Journal: Review
Journal Name Neuropharmacology
Volume 56
Issue Part SUPPL. 1
Page 18-31
Year of Publication 2009
Date of Publication 2009
NEURO 2009 <188>
Database EMBASE
Accession Number 2009000491
Authors Haydon P.G. Blendy J. Moss S.J. Rob Jackson F.
Institution
(Haydon, Moss) Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA
19104, United States.
(Blendy) Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104,
United States.
(Haydon, Moss, Rob Jackson) Department of Neuroscience, Tufts University School of Medicine, Boston, MA
02111, United States.
Country of Publication
United Kingdom
Title
Astrocytic control of synaptic transmission and plasticity: a target for drugs of
abuse?
Source
Neuropharmacology. 56(SUPPL. 1)(pp 83-90), 2009. Date of Publication: 2009.
Publisher
Elsevier Ltd
Abstract
It is well recognized that drugs of abuse lead to plastic changes in synapses and that these
long-term modifications have the potential to underlie adaptive changes of the brain that lead
to substance abuse. However the variety of molecular mechanisms involved in these
responses are not completely defined. We are just beginning to understand some of the roles
of glial cells that are associated with synapses. At many synapses an astrocyte process is
associated with pre- and postsynaptic neuron processes leading to the naming of this
synaptic structure as the Tripartite Synapse. Therefore, these glial cells are positioned so that
they influence synaptic transmission and thus could potentially regulate the actions of some
drugs of abuse. In mammalian systems there are correlations between long-term structural
changes in astrocytes and responses to drugs of abuse. However, whether such changes in
glia impact brain function and subsequent behaviors associated with addiction is poorly
understood. Studies using Drosophila show important roles of fly glia in mediating responses
to cocaine pointing to the potential for the involvement of mammalian glia in the brain's
responses to this as well as other drugs. In agreement with this possibility three receptor
systems known to be important in substance abuse, mGluR5, GABAB and CB-1 receptors,
are all expressed by astrocytes and the activation of these glial receptors is now known to
impact neuronal excitability and synaptic transmission. Given our new knowledge about the
presence of reciprocal signaling between astrocytes and synapses we are now at a time
when it becomes appropriate to determine how glial cells respond to drugs of abuse and
whether they contribute to the changes in brain function underlying substance abuse.
copyright 2008 Elsevier Ltd. All rights reserved.
ISSN 0028-3908
Publication Type Journal: Review
Journal Name Neuropharmacology
Volume 56
Issue Part SUPPL. 1
Page 83-90
Year of Publication 2009
Date of Publication 2009
NEURO 2009 <190>
Database EMBASE
Accession Number 2009000501
Authors Verdejo-Garcia A. Bechara A.
Institution
(Verdejo-Garcia) Department of Clinical Psychology, Institute of Neuroscience, Universidad de Granada, Spain.
(Bechara) Brain and Creativity Institute, University of Southern California, HEDCO Neuroscience Building, 3641
Watt Way, Suite B26, Los Angeles, CA 90089-2520, United States.
Country of Publication
United Kingdom
Title
A somatic marker theory of addiction.
Source
Neuropharmacology. 56(SUPPL. 1)(pp 48-62), 2009. Date of Publication: 2009.
Publisher
Elsevier Ltd
Abstract
Similar to patients with ventromedial prefrontal cortex (VMPC) lesions, substance abusers
show altered decision-making, characterized by a tendency to choose the immediate reward,
at the expense of negative future consequences. The somatic marker model proposes that
decision-making depends on neural substrates that regulate homeostasis, emotion and
feeling. According to this model, there should be a link between alterations in processing
emotions in substance abusers, and their impairments in decision-making. Growing evidence
from neuroscientific studies indicate that core aspects of addiction may be explained in terms
of abnormal emotional/homeostatic guidance of decision-making. Behavioral studies have
revealed emotional processing and decision-making deficits in substance abusers.
Neuroimaging studies have shown that altered decision-making in addiction is associated with
abnormal functioning of a distributed neural network critical for the processing of emotional
information, and the experience of "craving", including the VMPC, the amygdala, the striatum,
the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific
neurotransmitter systems that modulate activities of neural processes involved in decisionmaking. The aim of this paper is to review this growing evidence, and to examine the extent to
which these studies support a somatic marker theory of addiction. We conclude that there are
at least two underlying types of dysfunction where emotional signals (somatic markers) turn in
favor of immediate outcomes in addiction: (1) a hyperactivity in the amygdala or impulsive
system, which exaggerates the rewarding impact of available incentives, and (2) hypoactivity
in the prefrontal cortex or reflective system, which forecasts the long-term consequences of a
given action. copyright 2008 Elsevier Ltd. All rights reserved.
ISSN 0028-3908
Publication Type Journal: Review
Journal Name Neuropharmacology
Volume 56
Issue Part SUPPL. 1
Page 48-62
Year of Publication 2009
Date of Publication 2009
NEURO 2009 <191>
Database EMBASE
Accession Number 2009006611
Authors Romanova E.V. Hatcher N.G. Rubakhin S.S. Sweedler J.V.
Institution
(Romanova, Hatcher, Rubakhin, Sweedler) Department of Chemistry, Beckman Institute, University of Illinois, 600
South Mathews Avenue 63-5, Urbana, IL 61801, United States.
Country of Publication
United Kingdom
Title
Characterizing intercellular signaling peptides in drug addiction.
Source
Neuropharmacology. 56(SUPPL. 1)(pp 196-204), 2009. Date of Publication: 2009.
Publisher
Elsevier Ltd
Abstract
Intercellular signaling peptides (SPs) coordinate the activity of cells and influence organism
behavior. SPs, a chemically and structurally diverse group of compounds responsible for
transferring information between neurons, are broadly involved in neural plasticity, learning
and memory, as well as in drug addiction phenomena. Historically, SP discovery and
characterization has tracked advances in measurement capabilities. Today, a suite of
analytical technologies is available to investigate individual SPs, as well as entire intercellular
signaling complements, in samples ranging from individual cells to entire organisms.
Immunochemistry and in situ hybridization are commonly used for following preselected SPs.
Discovery-type investigations targeting the transcriptome and proteome are accomplished
using high-throughput characterization technologies such as microarrays and mass
spectrometry. By integrating directed approaches with discovery approaches, multiplatform
studies fill critical gaps in our knowledge of drug-induced alterations in intercellular signaling.
Throughout the past 35 years, the National Institute on Drug Abuse has made significant
resources available to scientists that study the mechanisms of drug addiction. The roles of
SPs in the addiction process are highlighted, as are the analytical approaches used to detect
and characterize them. copyright 2008 Elsevier Ltd. All rights reserved.
ISSN 0028-3908
Publication Type Journal: Review
Journal Name Neuropharmacology
Volume 56
Issue Part SUPPL. 1
Page 196-204
Year of Publication 2009
Date of Publication 2009
NEURO 2009 <192>
Database EMBASE
Accession Number 2009000498
Authors Bonci A. Borgland S.
Institution
(Bonci) Ernest Gallo Clinic, Research Center, University of California, San Francisco, United States.
(Bonci) Department of Neurology, University of California, San Francisco, United States.
(Borgland) Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Rm
212, 2176 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Country of Publication
United Kingdom
Title
Role of orexin/hypocretin and CRF in the formation of drug-dependent synaptic
plasticity in the mesolimbic system.
Source
Neuropharmacology. 56(SUPPL. 1)(pp 107-111), 2009. Date of Publication: 2009.
Publisher
Elsevier Ltd
Abstract
Dopamine neurons in the ventral tegmental area (VTA) play a very important role in a variety
of physiological as well as addictive behaviors. However, a clear understanding of the cellular
mechanisms underlying these behaviors is still missing. Within the VTA, recent studies have
shown that forms of synaptic plasticity such as long-term potentiation (LTP) and long-term
depression (LTD) are produced by drugs of abuse. The main goal of this review is to discuss
the relationship between plasticity at excitatory synapses in the VTA and addiction-associated
behaviors such as behavioral sensitization and cocaine self-administration. Furthermore,
recent studies have highlighted the role of orexin/hypocretin and corticotropin-releasing factor
(CRF) as powerful modulators of excitatory synaptic transmission in the VTA. Here, we will
discuss the potential correlation between the ability of these peptides in mediating excitatory
synaptic transmission and the development of stress- and drug-dependent behaviors. Taken
together, the results from the studies reviewed here shed new light on the mechanistic role of
plasticity at glutamatergic synapses in the VTA in mediating addictive, as well as stressdependent behaviors.
ISSN 0028-3908
Publication Type Journal: Review
Journal Name Neuropharmacology
Volume 56
Issue Part SUPPL. 1
Page 107-111
Year of Publication 2009
Date of Publication 2009
NEURO 2009 <196>
Database EMBASE
Accession Number 2009000485
Authors Aston-Jones G. Smith R.J. Moorman D.E. Richardson K.A.
Institution
(Aston-Jones, Smith, Moorman, Richardson) Department of Neurosciences, Medical University of South Carolina,
Basic Science Bldg. 403, 173 Ashley Ave., Charleston, SC 29425-5100, United States.
Country of Publication
United Kingdom
Title
Role of lateral hypothalamic orexin neurons in reward processing and addiction.
Source
Neuropharmacology. 56(SUPPL. 1)(pp 112-121), 2009. Date of Publication: 2009.
Publisher
Elsevier Ltd
Abstract
Orexins (also known as hypocretins) are recently discovered neuropeptides made
exclusively in hypothalamic neurons that have been shown to be important in
narcolepsy/cataplexy and arousal. Here, we conducted behavioral, anatomical and
neurophysiological studies that show that a subset of these cells, located specifically in lateral
hypothalamus (LH), are involved in reward processing and addictive behaviors. We found that
Fos expression in LH orexin neurons varied in proportion to preference for morphine, cocaine
or food. This relationship obtained both in drug naive rats and in animals during protracted
morphine withdrawal, when drug preference was elevated but food preference was
decreased. Recent studies showed that LH orexin neurons that project to ventral tegmental
area (VTA) have greater Fos induction in association with elevated morphine preference
during protracted withdrawal than non-VTA-projecting orexin neurons, indicating that the VTA
is an important site of action for orexin's role in reward processing. In addition, we found that
stimulation of LH orexin neurons, or microinjection of orexin into VTA, reinstated an
extinguished morphine preference. Most recently, using a self-administration paradigm we
discovered that the Ox1 receptor antagonist SB-334867 (SB) blocks cocaine-seeking induced
by discrete or contextual cues, but not by a priming injection of cocaine. Neurophysiological
studies revealed that locally applied orexin often augmented responses of VTA dopamine
(DA) neurons to activation of the medial prefrontal cortex (mPFC), consistent with the view
that orexin facilitates activation of VTA DA neurons by stimulus-reward associations. We also
recently showed that orexin in VTA is necessary for learning a morphine place preference.
These findings are consistent with results from others showing that orexin facilitates
glutamate-mediated responses, and is necessary for glutamate-dependent long-term
potentiation, in VTA DA neurons. We surmise from these studies that LH orexin neurons play
an important role in reward processing and addiction, and that LH orexin cells are an
important input to VTA for behavioral effects associated with reward-paired stimuli. copyright
2008 Elsevier Ltd. All rights reserved.
ISSN 0028-3908
Publication Type Journal: Review
Journal Name Neuropharmacology
Volume 56
Issue Part SUPPL. 1
Page 112-121
Year of Publication 2009
Date of Publication 2009
NEURO 2009 <198>
Database EMBASE
Accession Number 2009002882
Authors Kalivas P.W. LaLumiere R.T. Knackstedt L. Shen H.
Institution
(Kalivas, LaLumiere, Knackstedt, Shen) Department of Neurosciences, Medical University of South Carolina, 173
Ashley Ave, Charleston, SC 29464, United States.
Country of Publication
United Kingdom
Title
Glutamate transmission in addiction.
Source
Neuropharmacology. 56(SUPPL. 1)(pp 169-173), 2009. Date of Publication: 2009.
Publisher
Elsevier Ltd
Abstract
Cortico-striatal glutamate transmission has been implicated in both the initiation and
expression of addiction related behaviors, such as locomotor sensitization and drug-seeking.
While glutamate transmission onto dopamine cells in the ventral tegmental area undergoes
transient plasticity important for establishing addiction-related behaviors, glutamatergic
plasticity in the nucleus accumbens is critical for the expression of these behaviors. This
information points to the value of exploring pharmacotherapeutic manipulation of glutamate
plasticity in treating drug addiction. copyright 2008 Elsevier Ltd. All rights reserved.
ISSN 0028-3908
Publication Type Journal: Review
Journal Name Neuropharmacology
Volume 56
Issue Part SUPPL. 1
Page 169-173
Year of Publication 2009
Date of Publication 2009
NEURO 2009 <199>
Database EMBASE
Accession Number 2009000492
Authors Carlezon Jr. W.A. Thomas M.J.
Institution
(Carlezon Jr.) Behavioral Genetics Laboratory, Department of Psychiatry, Harvard Medical School, MRC 217, 115
Mill Street, Belmont, MA 02478, United States.
(Thomas) Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, United States.
(Thomas) Department of Psychology, University of Minnesota, Minneapolis, MN 55455, United States.
Country of Publication
United Kingdom
Title
Biological substrates of reward and aversion: A nucleus accumbens activity
hypothesis.
Source
Neuropharmacology. 56(SUPPL. 1)(pp 122-132), 2009. Date of Publication: 2009.
Publisher
Elsevier Ltd
Abstract
The nucleus accumbens (NAc) is a critical element of the mesocorticolimbic system, a brain
circuit implicated in reward and motivation. This basal forebrain structure receives dopamine
(DA) input from the ventral tegmental area (VTA) and glutamate (GLU) input from regions
including the prefrontal cortex (PFC), amygdala (AMG), and hippocampus (HIP). As such, it
integrates inputs from limbic and cortical regions, linking motivation with action. The NAc has
a well-established role in mediating the rewarding effects of drugs of abuse and natural
rewards such as food and sexual behavior. However, accumulating pharmacological,
molecular, and electrophysiological evidence has raised the possibility that it also plays an
important (and sometimes underappreciated) role in mediating aversive states. Here we
review evidence that rewarding and aversive states are encoded in the activity of NAc
medium spiny GABAergic neurons, which account for the vast majority of the neurons in this
region. While admittedly simple, this working hypothesis is testable using combinations of
available and emerging technologies, including electrophysiology, genetic engineering, and
functional brain imaging. A deeper understanding of the basic neurobiology of mood states
will facilitate the development of well-tolerated medications that treat and prevent addiction
and other conditions (e.g., mood disorders) associated with dysregulation of brain motivation
systems. copyright 2008 Elsevier Ltd. All rights reserved.
ISSN 0028-3908
Publication Type Journal: Review
Journal Name Neuropharmacology
Volume 56
Issue Part SUPPL. 1
Page 122-132
Year of Publication 2009
Date of Publication 2009
NEURO (A) 2009 <200>
Database EMBASE
Accession Number 2009000493
Authors Vezina P. Leyton M.
Institution
(Vezina) Department of Psychiatry, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637,
United States.
(Leyton) Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, Que. H3A 1A1, Canada.
Country of Publication
United Kingdom
Title
Conditioned cues and the expression of stimulant sensitization in animals and
humans.
Source
Neuropharmacology. 56(SUPPL. 1)(pp 160-168), 2009. Date of Publication: 2009.
Publisher
Elsevier Ltd
Abstract
Repeated intermittent exposure to psychostimulants can lead to long-lasting sensitization of
the drugs' behavioral and biochemical effects. Such findings have figured importantly in
recent theories of drug addiction proposing that sensitized nucleus accumbens (NAcc)
dopamine (DA) overflow in particular acts in concert with other alterations in the
neurochemistry of this nucleus to promote drug seeking and self-administration. Yet,
experiments in rodents, non-human primates and humans have not always detected
behavioral or biochemical sensitization following drug exposure, bringing into doubt the utility
of this model. In an effort to reconcile apparent discrepancies in the literature, this review
assesses conditions that might affect the expression of sensitization during testing.
Specifically, the role played by conditioned cues is reviewed. A number of reports strongly
support a potent and critical role for conditioned stimuli in the expression of sensitization.
Findings suggest that stimuli associated either with the presence or absence of drug can
respectively facilitate or inhibit sensitized responding. It is concluded that the presence or
absence of such stimuli during testing for sensitization in animal and human studies could
significantly affect the results obtained. It is necessary to consider this possibility especially
when interpreting the results of studies that fail to observe sensitized responding. copyright
2008 Elsevier Ltd. All rights reserved.
ISSN 0028-3908
Publication Type Journal: Review
Journal Name Neuropharmacology
Volume 56
Issue Part SUPPL. 1
Page 160-168
Year of Publication 2009
Date of Publication 2009
NEURO 2009 <201>
Database EMBASE
Accession Number 2009000490
Authors Falcon E. McClung C.A.
Institution
(Falcon, McClung) Department of Psychiatry, University of Texas, Southwestern Medical Center, 5323 Harry Hines
Boulevard, Dallas, TX 75390-9070, United States.
Country of Publication
United Kingdom
Title
A role for the circadian genes in drug addiction.
Source
Neuropharmacology. 56(SUPPL. 1)(pp 91-96), 2009. Date of Publication: 2009.
Publisher
Elsevier Ltd
Abstract
Diurnal and circadian rhythms are prominent in nearly all bodily functions. Chronic
disruptions in normal sleep wake and social schedules can lead to serious health problems
such as those seen in shift worker's syndrome. Moreover, genetic disruptions in normal
circadian gene functions have recently been linked to a variety of psychiatric conditions
including depression, bipolar disorder, seasonal affective disorder and alcoholism. Recent
studies are beginning to determine how these circadian genes and rhythms are involved in
the development of drug addiction. Several of these studies suggest an important role for
these genes in limbic regions of the brain, outside of the central circadian pacemaker in the
suprachiasmatic nucleus (SCN). This review summarizes some of the basic research into the
importance of circadian genes in drug addiction. copyright 2008 Elsevier Ltd. All rights
reserved.
ISSN 0028-3908
Publication Type Journal: Review
Journal Name Neuropharmacology
Volume 56
Issue Part SUPPL. 1
Page 91-96
Year of Publication 2009
Date of Publication 2009
NEURO 2009 <202>
Database EMBASE
Accession Number 2009000486
Authors Russo S.J. Mazei-Robison M.S. Ables J.L. Nestler E.J.
Institution
(Russo, Mazei-Robison, Ables, Nestler) Fishberg Department of Neuroscience, Mount Sinai School of Medicine,
One Gustave Levy Place, New York, NY 10029, United States.
Country of Publication
United Kingdom
Title
Neurotrophic factors and structural plasticity in addiction.
Source
Neuropharmacology. 56(SUPPL. 1)(pp 73-82), 2009. Date of Publication: 2009.
Publisher
Elsevier Ltd
Abstract
Drugs of abuse produce widespread effects on the structure and function of neurons
throughout the brain's reward circuitry, and these changes are believed to underlie the longlasting behavioral phenotypes that characterize addiction. Although the intracellular
mechanisms regulating the structural plasticity of neurons are not fully understood,
accumulating evidence suggests an essential role for neurotrophic factor signaling in the
neuronal remodeling which occurs after chronic drug administration. Brain-derived
neurotrophic factor (BDNF), a growth factor enriched in brain and highly regulated by several
drugs of abuse, regulates the phosphatidylinositol 3'-kinase (PI3K), mitogen-activated protein
kinase (MAPK), phospholipase Cgamma (PLCgamma), and nuclear factor kappa B
(NFkappaB) signaling pathways, which influence a range of cellular functions including
neuronal survival, growth, differentiation, and structure. This review discusses recent
advances in our understanding of how BDNF and its signaling pathways regulate structural
and behavioral plasticity in the context of drug addiction. copyright 2008 Elsevier Ltd. All
rights reserved.
ISSN 0028-3908
Publication Type Journal: Review
Journal Name Neuropharmacology
Volume 56
Issue Part SUPPL. 1
Page 73-82
Year of Publication 2009
Date of Publication 2009