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  • Title: Endogenous kappa-opioid mediation of stress-induced potentiation of ethanol-conditioned place preference and self-administration.
    Author: Sperling RE, Gomes SM, Sypek EI, Carey AN, McLaughlin JP.
    Journal: Psychopharmacology (Berl); 2010 Jun; 210(2):199-209. PubMed ID: 20401606.
    Abstract:
    RATIONALE: Exposure to inescapable stressors increases both the rewarding properties and self-administration of cocaine through the signaling of the kappa-opioid receptor (KOR), but the effect of this signaling on other reinforcing agents remains unclear. OBJECTIVE: The objective of this study is to test the hypothesis that signaling of the KOR mediates the forced swim stress (FSS)-induced potentiation of ethanol reward and self-administration. METHODS: Male C57Bl/6J mice were tested in a biased ethanol-conditioned place preference (CPP) procedure, and both C57Bl/6J and prodynorphin gene-disrupted (Dyn -/-) mice were used in two-bottle free choice (TBC) assays, with or without exposure to FSS. To determine the role of the KOR in the resulting behaviors, the KOR agonist U50,488 (10 mg/kg) and antagonist nor-binaltorphimine (nor-BNI, 10 mg/kg) were administered prior to parallel testing. RESULTS: C57Bl/6J mice exposed to repeated FSS 5 min prior to daily place conditioning with ethanol (0.8 g/kg) demonstrated a 4.4-fold potentiation of ethanol-CPP compared to unstressed mice that was prevented by nor-BNI pretreatment. Likewise, pretreatment with U50,488 90 min prior to daily ethanol place conditioning resulted in a 2.8-fold potentiation of ethanol-CPP. In the TBC assay, exposure to FSS significantly increased the consumption of 10% (v/v) ethanol by 19.3% in a nor-BNI-sensitive manner. Notably, Dyn -/- mice consumed a similar volume of ethanol as wild-type littermates and C57Bl/6J mice, but did not demonstrate significant stress-induced increases in consumption. CONCLUSIONS: These data demonstrated a stress-induced potentiation of the rewarding effects and self-administration of ethanol mediated by KOR signaling.
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