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Morphine and ethanol pretreatment effects on expression and extinction of ethanol-induced conditioned place preference and aversion in mice

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Abstract

Rationale

Opioid receptor antagonists reliably alter the expression or extinction of ethanol’s conditioned motivational effects as indexed by the place conditioning procedure, suggesting endogenous opioids are normally involved. These studies examined how exogenous stimulation of opioid receptors alters ethanol’s conditioned rewarding and aversive effects.

Objectives

Drugs that either directly (morphine) or indirectly (ethanol) stimulate opioid receptors were tested for their effects on the expression and extinction of ethanol-induced conditioned place preference (CPP) and conditioned place aversion (CPA).

Methods

Male DBA/2J mice were exposed to unbiased ethanol (2 g/kg) conditioning procedures that produced either CPP (experiments 1–2) or CPA (experiments 3–4). Morphine (0, 2.5, 5, or 10 mg/kg) was injected before three post-conditioning tests in experiments 1 and 3, whereas ethanol (0, 1, 2, or 3 g/kg) was injected before tests in experiments 2 and 4. All groups received vehicle on test 4 to determine whether the drug pretreatments altered the course of extinction.

Results

Morphine dose-dependently enhanced CPP expression (experiment 1), but ethanol dose-dependently reduced CPP expression (experiment 2). Test 4 showed no differences between drug-treated mice and mice given vehicle on all tests. Morphine had no effect on expression or extinction of ethanol-induced CPA (experiment 3). The highest ethanol dose (3 g/kg) interfered with CPA expression, but not extinction (experiment 4).

Conclusions

Pretreatment drug effects on ethanol CPP and CPA expression were most likely a byproduct of their activity altering effects rather than opioid-receptor mediated modulation of ethanol’s conditioned motivational effects. Neither drug affected the course of extinction.

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Acknowledgments

Research reported in this paper was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under award number R01AA007702. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, L470, Portland, OR, 97239-3098, USA

    Christopher L. Cunningham, Lindsey M. Schuette & Emily A. Young

  2. Department of Psychology, Linfield University, McMinnville, OR, 97128, USA

    Lee Bakner

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  1. Christopher L. Cunningham
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Correspondence to Christopher L. Cunningham.

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Cunningham, C.L., Bakner, L., Schuette, L.M. et al. Morphine and ethanol pretreatment effects on expression and extinction of ethanol-induced conditioned place preference and aversion in mice. Psychopharmacology 238, 55–66 (2021). https://doi.org/10.1007/s00213-020-05658-x

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