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

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

Fig. 1.

Mean percent time (± SEM) spent on the ethanol paired floor (collapsed over conditioning subgroup) during each 60 min extinction test after CPP conditioning in Experiment 1 (left panel). Mean activity rate (± SEM) during each test (right panel). Groups were pretreated with morphine (0, 2.5, 5 or 10 mg/kg) on “+” days, but were pretreated with saline on the “−” day (Day 4). Each group contained 23–24 mice. a = main effect of Dose (p < .005); b = main effect of Test (p < .05); c = interaction (p < .001)

Fig. 2.

Mean percent time (± SEM) spent on the ethanol paired floor (collapsed over conditioning subgroup) during each 60 min extinction test after CPP conditioning in Experiment 2 (left panel). Mean activity rate (± SEM) during each test (right panel). Groups were pretreated with ethanol (0, 1, 2 or 3 g/kg) on “+” days, but were pretreated with saline on the “−” day (Day 4). Each group contained 22–24 mice. a = main effect of Dose (p < .005); b = main effect of Test (p < .05); c = interaction (p < .001)

Fig. 3.

Mean percent time (± SEM) spent on the ethanol paired floor (collapsed over conditioning subgroup) during each 60 min extinction test after CPA conditioning in Experiment 3 (left panel). Mean activity rate (± SEM) during each test (right panel). Groups were pretreated with morphine (0, 2.5, 5 or 10 mg/kg) on “+” days, but were pretreated with saline on the “−” day (Day 4). Each group contained 24 mice. a = main effect of Dose (p < .001); b = main effect of Test (p < .05)

Fig. 4.

Mean percent time (± SEM) spent on the ethanol paired floor (collapsed over conditioning subgroup) during each 60 min extinction test after CPA conditioning in Experiment 4 (left panel). Mean activity rate (± SEM) during each test (right panel). Groups were pretreated with ethanol (0, 1, 2 or 3 g/kg) on “+” days, but were pretreated with saline on the “−” day (Day 4). Each group contained 24 mice. a = main effect of Dose (p < .001); b = main effect of Test (p < .001); c = interaction (p < .001)