ARTICLE IN PRESS
G Model
DAD-4246; No. of Pages 4
Drug and Alcohol Dependence xxx (2011) xxx–xxx
Contents lists available at SciVerse ScienceDirect
Drug and Alcohol Dependence
journal homepage: www.elsevier.com/locate/drugalcdep
Short communication
Naloxone-induced taste aversions in opiate-naïve Lewis and Fischer 344 rat
strains
Alexa G. Desko, Jennifer L. Cobuzzi ∗ , Anthony L. Riley
Psychopharmacology Laboratory, Department of Psychology, American University, 4400 Massachusetts Avenue, NW, Washington, DC 20016, United States
a r t i c l e
i n f o
Article history:
Received 14 July 2011
Received in revised form 9 September 2011
Accepted 17 September 2011
Available online xxx
Keywords:
LEW
F344
Naloxone
CTA
Drug abuse
a b s t r a c t
Background: The Lewis (LEW) and Fischer (F344) rat strains appear differentially sensitive to the aversive
effects of several used and abused drugs. Naloxone, a mu opioid receptor antagonist that induces aversions
in outbred rats but has no abuse potential, was assessed to determine the characteristics of compounds
for which the strains differ.
Methods: Opioid-naïve male LEW and F344 rats were given access to saccharin followed by low (Experiment 1) and high (Experiment 2) doses of naloxone every 4th day for five pairings. Aversions were
assessed in both one-bottle and two-bottle tests.
Results: In Experiment 1, aversions were evident at 10 mg/kg (one-bottle) and at 5.6 and 10 mg/kg (twobottle) with no apparent strain difference for either assessment. In Experiment 2, aversions were evident
for LEW animals (but not F344) at 18 and 32 mg/kg (one-bottle). LEW animals injected with 32 mg/kg
displayed greater aversions than F344 animals receiving the same dose. Both strains displayed aversions
at all doses in the two-bottle test with no strain difference.
Conclusions: Naloxone induced aversions that were strain dependent only at specific doses and under
the one-bottle testing condition. These results parallel those of several other used and abused drugs but
differ dramatically from those seen with morphine in the two strains (F344 > LEW). Further assessments
utilizing the LEW–F344 model should investigate other drugs to establish the set of compounds for which
the strains differ and to characterize the mechanism underlying the observed differences.
© 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
Although the Lewis (LEW) and Fischer (F344) inbred rat strains
are well characterized in terms of their relative sensitivity to the
rewarding effects of a variety of drugs of abuse (LEW > F344; see
Kosten and Ambrosio, 2002; Riley et al., 2009), they also differ in
their sensitivity to their aversive effects (see Riley et al., 2009). For
example, the F344 strain displays stronger morphine-, nicotineand ethanol-induced aversions (Lancellotti et al., 2001; Pescatore
et al., 2005; Roma et al., 2006), while the LEW strain displays greater
aversions induced by cocaine and caffeine (Glowa et al., 1994;
Vishwanath et al., 2011). Given that drug use and abuse vulnerability is a function of the balance between the drug’s rewarding
and aversive effects (Riley et al., 2009; Riley, 2011), strain differences in the aversive properties of drugs may provide insight into
the role of genotype in such effects.
The LEW and F344 strains have been reported to have basal
neurochemical and neuroanatomical differences in brain systems
mediating responsivity to the opioids, particularly in the nucleus
∗ Corresponding author. Tel.: +1 202 885 1721; fax: +1 202 885 1081.
E-mail address: jc9378a@american.edu (J.L. Cobuzzi).
accumbens (NAc) and locus coeruleus (LC) (Guitart et al., 1992,
1993). For example, the LEW strain displays lower basal levels
of proenkephalin mRNA in the ventro- and dorsolateral caudate
putamen (Sánchez-Cardoso et al., 2007), as well as lower levels
of dynorphin A and B and leu-enkephalin Arg6 in the striatum
(Nylander et al., 1995). Further, the LEW and F344 strains have differential basal expression of intracellular G-proteins (F344 > LEW)
and cAMP-dependent signaling (LEW > F344; Guitart et al., 1993)
as well as differential levels of tyrosine hydroxylase (TH) in the LC
(LEW > F344; Guitart et al., 1992). Given that these brain areas and
systems may mediate the affective response to both natural and
non-natural reinforcers (Koob and Nestler, 1997), these areas may
play a role in the differential reactivity of the LEW and F344 strains
in response to opioid administration. It then might be expected that
the behavior of the two strains might also differ when these systems are blocked or deactivated in opioid-naïve animals. Although
such an assessment has not been made in the LEW and F344 strains,
administration of the opiate antagonist naloxone to opioid-naïve
outbred rats induces a dose-dependent conditioned taste aversion
at doses as low as 1, 3.2 and 10 mg/kg IP (Stolerman et al., 1978; see
also Frenk and Rogers, 1979; Leshem, 1984), presumably as a result
of functional alterations in endogenous opioid systems (Mucha and
Walker, 1987; Mucha and Herz, 1985; Mucha et al., 1985).
0376-8716/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.drugalcdep.2011.09.016
Please cite this article in press as: Desko, A.G., et al., Naloxone-induced taste aversions in opiate-naïve Lewis and Fischer 344 rat strains. Drug
Alcohol Depend. (2011), doi:10.1016/j.drugalcdep.2011.09.016
G Model
DAD-4246; No. of Pages 4
ARTICLE IN PRESS
A.G. Desko et al. / Drug and Alcohol Dependence xxx (2011) xxx–xxx
2
Interestingly, the classical emetic LiCl induces comparable dosedependent aversions in the two strains (see Foynes and Riley, 2004),
suggesting that some feature of drugs that are used and/or abused
may be important in these strain differences. To address this possibility, the present studies examined the ability of the mu opioid
antagonist naloxone to induce strain-dependent aversions. Naloxone induces aversions in outbred rats (Frenk and Rogers, 1979;
Hunt et al., 1983; Leshem, 1984; Stolerman et al., 1978) and like LiCl,
has little abuse liability and has emetic effects (see Crampton and
Daunton, 1983; Bhargava et al., 1981). Given this, naloxone allows
for the characterization of the nature of compounds for which the
LEW and F344 strains differ. Accordingly, opiate-naïve LEW and
F344 rats were given saccharin and then injected with various doses
of naloxone (0, 3.2, 5.6, 10 mg/kg: Experiment 1; 0, 10, 18, 32 mg/kg:
Experiment 2) to assess strain differences in its aversive effects.
2. Methods
2.1. Experiment 1: low-dose naloxone
2.1.1. Subjects. Subjects in Experiment 1 were 71 experimentally naïve LEW (n = 36)
and F344 (n = 35) male rats (Harlan, Indianapolis), 90 days old and 247 g (LEW) and
185 g (F344). They were run in two replicates (n = 15 and 14: Replicate 1; n = 21 and
21: Replicate 2). Subjects in the replicates did not differ [F(1,63) = 0.283, p = 0.597],
and data were pooled for analysis and presentation. Animals were housed in individual wire-mesh cages and maintained on a 12:12 h cycle (lights on at 08:00 h) and
at an ambient temperature of 23 ◦ C. Except where noted, food and water were provided ad libitum. Fluids were presented in 50 ml graduated Nalgene tubes. Animals
were handled 2 weeks prior to the initiation of experimental manipulations to minimize handling stress. All manipulations were performed in the light phase of the
light/dark cycle and were in compliance with the National Research Council (1996)
and approved by the Institutional Animal Care and Use Committee at American
University.
2.1.2. Drugs and solutions. Naloxone HCl (supplied by NIDA) was dissolved in isotonic saline (1.0 mg/ml; Sigma) and administered intraperitoneally (ip). Sodium
saccharin (0.1%; Sigma) was prepared as a 1 g/l solution in tap water.
2.1.3. Conditioned taste aversion.
2.1.3.1. Phase I: habituation. Following 232/3 h water deprivation, rats were given
20 min water access. This was repeated daily until consumption stabilized.
2.1.3.2. Phase II: conditioning. On Day 1 of this phase, subjects were given 20 min
access to saccharin. Immediately following, subjects within each strain were
assigned to four groups such that saccharin consumption was comparable and given
an ip injection of 0, 3.2, 5.6 or 10.0 mg/kg naloxone, yielding Groups L0 (n = 8), L3.2
(n = 8), L5.6 (n = 9), L10 (n = 11) F0 (n = 8), F3.2 (n = 8), F5.6 (n = 10) and F10 (n = 9).
The letter denotes the strain; the number indicates the dose of naloxone. On the
following 3 days, subjects were given 20 min water access. This cycle was repeated
five times. The fifth saccharin trial served as a one-bottle test of the acquisition of
the aversion to saccharin.
2.1.3.3. Phase III: two-bottle aversion test. On the day following the last cycle of
Phase II, subjects were given 20 min access to water and saccharin in a two-bottle
test of the aversion. The location of the bottles was counterbalanced within each
group. Saccharin was initially presented for 5 s. Then, saccharin was removed and
water was presented for 5 s. Both bottles were then presented for the remainder of
the session. Saccharin preference was calculated as the percent saccharin of total
consumption.
2.2. Experiment 2: high-dose naloxone
2.2.1. Subjects. Subjects in Experiment 2 were 66 experimentally naïve LEW (n = 34)
and F344 (n = 32) subjects of the same sex, strain and age and maintained under the
same conditions as in Experiment 1. Subjects were run in two replicates (n = 17
and 17: Replicate 1; n = 17 and 15: Replicate 2). Subjects in the replicates did not
differ [F(1,58) = 5.049, p = 0.565], and data were pooled for analysis and presentation.
The procedures in this phase were identical to Experiment 1 with the following
exception: during conditioning, subjects in each strain were injected with 0, 10, 18
or 32 mg/kg naloxone, yielding Groups L0 (n = 8), L10 (n = 8), L18 (n = 9), L32 (n = 9),
F0 (n = 7), F10 (n = 7), F18 (n = 9) and F32 (n = 9).
Fig. 1. Top panel: Mean (±SEM) saccharin consumption (ml) on the one-bottle
aversion test (Trial 5) in which LEW (open bars) and F344 (solid bars) animals
were given saccharin paired with varying low doses of naloxone (0, 0.32, 5.6
or 10 mg/kg). *Collapsed across strain, animals injected with 10 mg/kg naloxone consumed significantly less saccharin than animals injected with vehicle.
Bottom panel: Mean (±SEM) saccharin preference (%) for the LEW (open bars)
and F344 (solid bars) animals on the two-bottle aversion test of Experiment 1.
#
Collapsed across strain, animals injected with 5.6 and 10 mg/kg naloxone consumed significantly less saccharin than animals injected with vehicle. ∧ Collapsed
across dose, LEW animals consumed significantly less saccharin than F344
animals.
2.3. Analysis
For each experiment, differences in mean saccharin consumption on the onebottle aversion test (Trial 5) were analyzed using a 2 × 4 univariate ANOVA with
between-subjects factors of Strain (LEW; F344) and Dose (0, 3.2, 5.6; 10 mg/kg:
Experiment 1; 0, 10, 18; 32 mg/kg: Experiment 2). Differences in mean saccharin
preference on the two-bottle aversion test were compared using a 2 × 4 univariate
ANOVA with between-subjects factors of Strain and Dose. All pair-wise comparisons were made using one-way ANOVAs followed by Tukey’s HSD post hoc tests;
significance was assessed at ˛ ≤ 0.05.
3. Results
3.1. Experiment 1: low-dose naloxone
3.1.1. Mean saccharin consumption – one-bottle aversion test. The
2 × 4 univariate ANOVA on the one-bottle test (Trial 5) revealed
a significant effect of Dose [F(3,63) = 15.790, p < 0.01]. Collapsed
across strain, animals injected with 10 mg/kg naloxone consumed
significantly less saccharin than animals injected with vehicle
(p < 0.01; see Fig. 1; top panel). There was no significant effect of
Strain or a Strain × Dose interaction.
Please cite this article in press as: Desko, A.G., et al., Naloxone-induced taste aversions in opiate-naïve Lewis and Fischer 344 rat strains. Drug
Alcohol Depend. (2011), doi:10.1016/j.drugalcdep.2011.09.016
G Model
DAD-4246; No. of Pages 4
ARTICLE IN PRESS
A.G. Desko et al. / Drug and Alcohol Dependence xxx (2011) xxx–xxx
3
3.1.2. Saccharin preference – two-bottle aversion test. The 2 × 4 univariate ANOVA on the two-bottle test revealed significant effects of
Strain [F(1,63) = 4.182, p < 0.05] and Dose [F(3,63) = 4.567, p < 0.01]
but no Strain × Dose interaction [F(3,63) = 1.209, p = 0.314]. Collapsed across dose, the percent saccharin consumed by LEW
animals was significantly less than that of the F344 animals. Collapsed across strain, the percent saccharin consumed by animals
injected with 5.6 and 10 mg/kg naloxone was significantly less
than that of vehicle-injected animals (p’s < 0.05; see Fig. 1; bottom
panel).
3.2. Experiment 2: high dose naloxone
3.2.1. Mean saccharin consumption – one-bottle aversion test. The
2 × 4 univariate ANOVA on the one-bottle aversion test (Trial 5)
revealed significant effects of Strain [F(1,58) = 8.644, p < 0.01]
and Dose [F(3,58) = 14.355, p < 0.001] as well as a significant
Strain × Dose interaction [F(3,58) = 3.084, p < 0.05]. LEW animals
injected with 18 and 32 mg/kg naloxone consumed significantly
less saccharin than vehicle-injected animals of their own strain
(both p’s ≤ 0.01), indicative of the development of aversions at the
higher doses of naloxone relative to vehicle-injected controls. F344
animals did not differ from vehicle-injected controls at any dose
tested. At 32 mg/kg, LEW animals consumed significantly less saccharin than F344 animals (p < 0.01; see Fig. 2; top panel).
3.2.2. Saccharin preference – two-bottle aversion test. The 2 × 4
univariate ANOVA revealed an effect of Dose [F(3,58) = 19.173,
p < 0.001]. There was no effect of Strain or Strain × Dose interaction [F(3,58) = 0.284, p = 0.837]. Collapsed across strain, the percent
saccharin consumed by animals injected with 10, 18 and 32 mg/kg
naloxone was significantly less than that of vehicle-injected animals (p’s < 0.0001; see Fig. 2; bottom panel).
4. Discussion
A variety of used and abused compounds differentially induce
taste aversions in the LEW and F344 rat strains, the exception being
LiCl (see Foynes and Riley, 2004). Given that naloxone induces taste
aversions and has no abuse potential, it provides an assessment of
whether use and abuse are necessary conditions for such differences. In the one-bottle aversion test in Experiment 1, naloxone
induced aversions at the 10 mg/kg dose relative to vehicle controls with no effect of strain. Aversions were evident at both 5.6
and 10 mg/kg on the more sensitive two-bottle test (see Batsell
and Best, 1993), but again there were no strain differences. In the
one-bottle test in Experiment 2, naloxone induced aversions at 18
and 32 mg/kg in the LEW strain (relative to LEW animals administered vehicle). No dose of naloxone induced aversions in the F344
strain in this assessment. Additionally, the amount consumed by
the LEW subjects injected with 32 mg/kg naloxone was significantly
less than that of F344 subjects injected at this dose. All of the higher
doses of naloxone induced aversions in the two-bottle test, but
there were no strain differences in the degree of the aversion.
Although the two strains did differ in naloxone-induced taste
aversions, these differences were modest and evident only under
specific parametric conditions, e.g., at the highest dose and only
in the one-bottle test. Such small, dose-dependent differences
have been reported with a number of other compounds, including cocaine, nicotine, alcohol and caffeine (Glowa et al., 1994;
Lancellotti et al., 2001; Pescatore et al., 2005; Roma et al., 2006;
Vishwanath et al., 2011; for similar effects in other behavioral
preparations, see Kosten and Ambrosio, 2002). That the strain difference was not evident on the two-bottle aversion test is likely due
to the fact that the sensitivity of this test often precludes observing
differences among groups, i.e., it can detect aversions not evident
Fig. 2. Top panel: Mean (±SEM) saccharin consumption (ml) on the one-bottle aversion test (Trial 5) in which LEW (open bars) and F344 (solid bars) animals were given
saccharin paired with varying high doses of naloxone (0, 10, 18 or 32 mg/kg). *LEW
animals injected with 18 and 32 mg/kg naloxone consumed significantly less saccharin than LEW animals injected with vehicle. # LEW animals injected with 32 mg/kg
naloxone consumed significantly less saccharin than F344 animals injected with
32 mg/kg naloxone. Bottom panel: Mean (±SEM) saccharin preference (%) for the
LEW (open bars) and F344 (solid bars) animals on the two-bottle aversion test of
Experiment 2. ∧ Collapsed across strain, animals injected with 10, 18 and 32 mg/kg
naloxone consumed significantly less saccharin than animals injected with vehicle.
in less sensitive designs, but is too sensitive to reveal graded effects
(see Rinker et al., 2011 for a recent discussion of this issue; see also
Batsell and Best, 1993).
Although the effects with naloxone parallel those reported for a
variety of other compounds (see above), the direction of the difference is highly drug-dependent. For example, the F344 strain
shows greater aversions than the LEW strain with nicotine and
alcohol, whereas the LEW strain displays greater aversions than
the F344 strain with cocaine and caffeine. In relation to the current effects with naloxone, it is interesting that the effects reported
here (LEW > F344) are opposite to those reported with morphine
(F344 > LEW; see Lancellotti et al., 2001; Davis et al., 2009). In
attempting to understand the basis for such effects, it is important to note that the LEW and F344 rat strains differ significantly in
the neurochemical systems mediating opiate-induced effects (both
endogenous and exogenous). For example, the LEW strain has lower
levels of proenkephalin mRNA in the ventro- and dorsolateral caudate putamen (Sánchez-Cardoso et al., 2007), dynorphin A and B
and leu-enkephalin Arg6 in the striatum (Nylander et al., 1995) as
well as levels of intracellular G-proteins relative to F344 animals
(Guitart et al., 1993). LEW animals also display higher levels of TH,
cAMP-dependent protein kinase signaling and adenylate cyclase in
Please cite this article in press as: Desko, A.G., et al., Naloxone-induced taste aversions in opiate-naïve Lewis and Fischer 344 rat strains. Drug
Alcohol Depend. (2011), doi:10.1016/j.drugalcdep.2011.09.016
G Model
DAD-4246; No. of Pages 4
ARTICLE IN PRESS
A.G. Desko et al. / Drug and Alcohol Dependence xxx (2011) xxx–xxx
4
the LC than F344 animals (Guitart et al., 1992, 1993). These basal
differences have been discussed relative to their role in a variety of
behavioral effects reported in the F344 and LEW strains (see Kosten
and Ambrosio, 2002; Sánchez-Cardoso et al., 2007); however, their
role in the differential aversions induced by naloxone is less clear. It
has been argued (see Mucha et al., 1985; Stolerman, 1985) that the
effects of naloxone administration in opiate-naïve animals is a function of homeostatic dysregulation in basal endorphin activity (i.e.,
basal opioid tone; see also Eisenberg, 1980; Frenk and Rogers, 1979)
that produces an aversive state. Given this and the differing basal
opioid activity of the two strains, it is possible that the antagonism
of the different neurochemical systems mediating opioid activity
in the two strains mediates their differential responsivity to naloxone (as indexed in the taste aversion design). What would remain
to be explained is why the differences between the strains vary
with agonist or antagonist administration. As noted, morphine is
more aversive in the F344 than the LEW strain, whereas naloxone
is more aversive in the LEW than the F344 strain. These differences
suggest that the basal opioid conditions that mediate the sensitivity to the agonist may impact antagonist sensitivity, although the
mechanism for such an effect remains unknown. In the absence of
opioid binding profiles in the two strains, it is unknown if the affinity of morphine and naloxone in the two strains differ and if such
differences (if they do exist) mediate the differential reactivity seen
in the aversion design.
The purpose of the present series of experiments was to assess
aversions induced by naloxone in the two strains and provide additional characterization of compounds on which the LEW and F344
strains may differ. As noted above, only compounds used and/or
abused in humans and animal models have been reported to differentially induce aversions in these strains (the only exception to
these differential effects being LiCl). The fact that strain differences
were evident with naloxone suggests that the differential effects
of drugs in these strains are not limited to drugs with rewarding properties, although the basis for the effects reported here are
unknown. The present findings argue for assessments with other
drugs to establish the range of compounds for which the strains
differ and to characterize the basis for these differences. Additionally, neurobiological assessments of the reactivity of the LEW and
F344 opioidergic systems are necessary in order to determine what
role, if any, the reported basal differences and differential reactivity of these systems play in their response to naloxone. Given
the role inbred strains play in isolating potential genetic factors in
behavior, such information may be useful in determining if and to
what extent genetic differences in sensitivity to the effects of drugs
contribute to behavioral differences.
Role of funding source
This research was supported by a grant from the Mellon Foundation to A.L.R. The Mellon Foundation had no further role in the study
design, data collection, analysis and interpretation, the writing of
the report, or the decision to submit the manuscript for publication.
Contributors
A.G.D., J.L.C and A.L.R. participated in the design and coordination of the study, performed the analysis and drafted up the
manuscript. A.G.D. performed all data collection. All authors contributed to and have approved the final manuscript.
Conflict of interest
No conflict declared.
References
Batsell, W.R., Best, M.R., 1993. One bottle too many? Method of testing determines
the detection of overshadowing and retention of taste aversions. Anim. Learn.
Behav. 21, 154–158.
Bhargava, K.P., Dixit, K.S., Gupta, Y.K., 1981. Enkephalin receptors in the emetic
chemoreceptor trigger zone of the dog. Br. J. Pharmacol. 72, 471–475.
Crampton, G.H., Daunton, N.G., 1983. Systemic naloxone increases the incidence of
motion sickness in the cat. Pharmacol. Biochem. Behav. 19, 827–829.
Davis, C.M., Rice, K.C., Riley, A.L., 2009. Opiate-agonist induced taste aversion learning in the Fischer 344 and Lewis rat strains: evidence for differential mu opioid
receptor activation. Pharmacol. Biochem. Behav. 93, 397–405.
Eisenberg, R.M., 1980. Effects of naloxone on plasma corticosterone in the opiatenaïve rat. Life Sci. 26, 935–943.
Foynes, M.M., Riley, A.L., 2004. Lithium-chloride-induced conditioned taste aversions in the Lewis and Fischer 344 rat strains. Pharmacol. Biochem. Behav. 79,
303–308.
Frenk, H., Rogers, G.H., 1979. The suppressant effects of naloxone on food and water
intake in the rat. Behav. Neural Biol. 26, 23–40.
Glowa, J.R., Shaw, A.E., Riley, A.L., 1994. Cocaine-induced conditioned taste
aversions: comparisons between effects in LEW/N and F344/N rat strains. Psychopharmacology 114, 229–232.
Guitart, X., Kogan, J.H., Berhow, M., Terwilliger, R.Z., Aghajanian, G.K., Nestler, E.J.,
1993. Lewis and Fischer rat strains display differences in biochemical, electrophysiological and behavioral parameters: studies in the nucleus accumbens and
locus coeruleus of drug naive and morphine-treated animals. Brain Res. 611,
7–17.
Guitart, X., Beitner-Johnson, D., Marby, D.W., Kosten, T.A., Nestler, E.J., 1992. Fischer
and Lewis rat strains differ in basal levels of neurofilament proteins and their
regulation by chronic morphine in the mesolimbic dopamine system. Synapse
12, 242–253.
Hunt, T., Amit, Z., Switzman, L., Sinyor, D., 1983. An aversive naloxone-morphine
interaction in rats. Neurosci. Lett. 35, 311–315.
Koob, G.F., Nestler, E.J., 1997. The neurobiology of drug addiction. J. Neuropsychiatry
Clin. Neurosci. 9, 482–497.
Kosten, T.A., Ambrosio, E., 2002. HPA axis function and drug addictive behaviors:
insights from studies with Lewis and Fischer 344 inbred rats. Psychoneuroendocrinology 27, 35–69.
Lancellotti, D., Bayer, B.M., Glowa, J.R., Houghtling, R.A., Riley, A.L., 2001. Morphineinduced conditioned taste aversions in the LEW/N and F344/N rat strains.
Pharmacol. Biochem. Behav. 68, 603–610.
Leshem, M., 1984. Suppression of feeding by naloxone in rat: a dose-response comparison of anorexia and conditioned taste aversion suggesting a specific anorexic
effect. Psychopharmacology 82, 127–130.
National Research Council, 1996. Guidelines for the Care and Use of Laboratory
Animals. National Academy Press, Washington, DC, pp. 1–125.
Mucha, R.F., Walker, M.J.K., 1987. Aversive property of opioid receptor blockade in
drug-naive mice. Psychopharmacology 93, 483–488.
Mucha, R.F., Herz, A., 1985. Motivational properties of kappa and mu opioid receptor
agonists studied with place and taste preference conditioning. Psychopharmacology 86, 274–280.
Mucha, R.F., Millan, M.J., Herz, A., 1985. Aversive properties of naloxone in
non-dependent (naive) rats may involve blockade of central beta-endorphin.
Psychopharmacology 86, 281–285.
Nylander, I., Vlaskovska, M., Terenius, L., 1995. Brain dynorphin and enkephalin systems in Fischer and Lewis rats: effects of morphine tolerance and withdrawal.
Brain Res. 683, 25–35.
Pescatore, K.A., Glowa, J.R., Riley, A.L., 2005. Strain differences in the acquisition of
nicotine-induced conditioned taste aversion. Pharmacol. Biochem. Behav. 82,
751–757.
Riley, A.L., 2011. The paradox of drug taking: the role of the aversive effects of drugs.
Physiol. Behav. 103, 69–78.
Riley, A.L., Davis, C.M., Roma, P.G., 2009. Strain differences in taste aversion learning: implications for animal models of drug abuse. In: Reilly, S., Schachtman,
T.R. (Eds.), Conditioned Taste Aversion: Behavioral and Neural Processes. Oxford
University Press, New York, pp. 226–261.
Rinker, J.A., Hutchison, M.A., Chen, S.A., Thorsell, A., Heilig, M., Riley, A.L., 2011. Exposure to nicotine during periadolescence or early adulthood alters aversive and
physiological effects induced by ethanol. Pharmacol. Biochem. Behav. 99, 7–16.
Roma, P.G., Flint, W.W., Higley, J.D., Riley, A.L., 2006. Assessment of the aversive and
rewarding effects of alcohol in Fischer and Lewis rats. Psychopharmacology 189,
187–199.
Sánchez-Cardoso, P., Higuera-Matas, A., Martin, S., del Olmo, N., Miguens, M., GarciaLecumberri, C., Ambrosio, E., 2007. Modulation of the endogenous opioid system
after morphine self-administration and during its extinction: a study in Lewis
and Fischer 344 rats. Neuropharmacology 52, 931–948.
Stolerman, I.P., 1985. Motivational effects of opioids: evidence on the role of endorphins in mediating reward or aversion. Pharmacol. Biochem. Behav. 23, 877–881.
Stolerman, I.P., Pilcher, C.W.T., D’Mello, G.D., 1978. Stereospecific aversive property
of narcotic antagonists in morphine-free rats. Life Sci. 22, 1755–1762.
Vishwanath, J.M., Desko, A.G., Riley, A.L., 2011. Caffeine-induced taste aversions in
Lewis and Fischer rat strains: differential sensitivity to the aversive effects of
drugs. Pharmacol. Biochem. Behav. 100, 66–72.
Please cite this article in press as: Desko, A.G., et al., Naloxone-induced taste aversions in opiate-naïve Lewis and Fischer 344 rat strains. Drug
Alcohol Depend. (2011), doi:10.1016/j.drugalcdep.2011.09.016