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Neuroscience. 2013 Sep 26;249:214-22. doi: 10.1016/j.neuroscience.2012.12.028. Epub 2012 Dec 29.

Stress, κ manipulations, and aversive effects of ethanol in adolescent and adult male rats.

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Center for Development and Behavioral Neuroscience, Department of Psychology, Binghamton University, 4400 Vestal Parkway East, Binghamton, NY 13902-6000, USA.


Elevated ethanol use during adolescence, a potentially stressful developmental period, is accompanied by insensitivity to many aversive effects of ethanol relative to adults. Given evidence that supports a role for stress and the kappa opioid receptor (KOR) system in mediating aversive properties of ethanol and other drugs, the present study assessed the role of KOR antagonism by nor-binaltorphimine (nor-BNI) on ethanol-induced conditioned taste aversion (CTA) in stressed (exposed to repeated restraint) and non-stressed male rats (Experiment 1), with half of the rats pretreated with nor-BNI before stressor exposure. In Experiment 2, CTA induced by the kappa agonist U62,066 was also compared in stressed and non-stressed adolescents and adults. A highly palatable solution (chocolate Boost) was used as the conditioned stimulus (CS), thereby avoiding the need for water deprivation to motivate consumption of the CS during conditioning. No effects of stress on ethanol-induced CTA were found, with all doses eliciting aversions in adolescents and adults in both stress conditions. However, among stressed subjects, adults given nor-BNI before the repeated stressor displayed blunted ethanol aversion relative to adults given saline at that time. This effect of nor-BNI was not seen in adolescents, findings that support a differential role for the KOR involvement in ethanol CTA in stressed adolescents and adults. Results from Experiment 2 revealed that all doses of U62,066 elicited aversions in non-stressed animals of both ages that were attenuated in stressed animals, findings that support a modulatory role for stress in aversive effects of KOR activation. Collectively, these results suggest that although KOR sensitivity appears to be reduced in stressed subjects, this receptor system does not appear to contribute to age differences in ethanol-induced CTA under the present test circumstances.


ANOVA; CPA; CPP; CS; CTA; DA; DYN; KOR; MOR; adolescence; analysis of variance; conditioned place aversion; conditioned place preference; conditioned stimulus; conditioned taste aversion; dopamine; dynorphins; ethanol; kappa opioid receptor; mu opioid receptor; nor-BNI; nor-binaltorphimine; rat; stress

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