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ORIGINAL INVESTIGATION

Morphine and ethanol pretreatment effects on expression and extinction of ethanol-induced conditioned place preference and aversion in mice Christopher L. Cunningham 1 & Lee Bakner 2 & Lindsey M. Schuette 1 & Emily A. Young 1 Received: 26 February 2020 / Accepted: 7 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

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. Keywords Conditioned place preference . Conditioned place aversion . Ethanol . Morphine . Opioid . Reward . Aversion . Conditioning . Locomotor activity . Inbred mice (DBA/2J)

Introduction The opioid system has been strongly implicated in the acute and chronic effects of ethanol for many decades (Blum and Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00213-020-05658-x) contains supplementary material, which is available to authorized users. * Christopher L. Cunningham [email protected] 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

2

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

Payne 1991). Its role in such effects has been repeatedly supported by studies showing that pretreatmen