mu-opioid receptor knockout mice do not self-administer alcohol

Opioid peptides long have been hypothesized to play a role in ethanol reinf orcement. Neuropharmacological studies have shown that opioid receptor anta gonists decrease ethanol self-administration in rodents and prevent relapse in humans. However, the exact mechanism for such powerful effects has rema ined elusive. The availability of mu-opioid receptor knockout mice has made possible the direct examination of the role of the mu-opioid receptor in m ediating ethanol self-administration. In the present experiments, both nose poke and lever operant ethanol self-administration and several tests of two bottle-choice ethanol drinking were studied in these genetically engineere d mice. In no case did knockout mice show evidence of ethanol self-administ ration, and, in fact, these mice showed evidence of an aversion to ethanol under several experimental conditions. These data provide new evidence for a critical role for mu-opioid receptors in ethanol self-administration asse ssed with a variety of behavioral paradigms and new insights into the neuro pharmacological basis for ethanol reinforcement.