Increased ethanol self-administration in δ-opioid receptor knockout mice

Background: The role of the delta -opioid receptor in ethanol drinking has remained unclear despite the use of traditional pharmacological and correlational approaches. The results of several studies suggest that pharmacological blockade of these receptors results in decreases in ethanol drinking behavior, but an approximately equal number of reports have failed to observe an effect of delta -receptor antagonism on ethanol drinking. It is clear that alternative approaches to understanding opioid-receptor involvement in ethanol drinking are needed. Methods: In this study, ethanol drinking was examined in delta -opioid receptor knockout (KO) mice by using first a two-bottle-choice test, then an operant self-administration paradigm and a second two-bottle-choice test, in that order. In addition, because KO mice were previously shown to display enhanced anxiety-like behavior relative to wild-type (WT) mice, the effect of ethanol self-administration on anxiety-like responses was determined. Results: delta KO mice initially showed no evidence of a preference for ethanol in the first two-bottle-choice drinking test; however, after an experience of operant self-administration of ethanol, a preference for ethanol developed in the second two-bottle-choice test. KO mice also showed a preference for ethanol over water and self-administered more ethanol than WT mice in the operant self-administration paradigm. The ethanol self-administered in this procedure was sufficient to reverse the innate anxiety-like response observed in this strain. Conclusions: delta KO mice showed a greater preference for ethanol and consumed more ethanol than their WT counterparts, suggesting that a decrease in delta -receptor activity is associated with increased ethanol-drinking behavior. It is hypothesized that delta receptors may influence ethanol self-administration at least partly through an effect of these receptors on anxiety-like behavior.