The κ-opioid receptor antagonist JDTic decreases ethanol intake in alcohol-preferring AA rats.

Abstract

Studies suggest that the κ-opioidergic system becomes overactivated as ethanol use disorders develop. Nalmefene, a currently approved treatment for ethanol use disorders, may also elicit some of its main effects via the κ-opioidergic system. However, the exact role of κ-opioid receptors on regulating ethanol intake and contribution to the development of ethanol addiction remains to be elucidated. The aim of the present study was to clarify the role of accumbal κ-opioid receptors in controlling ethanol intake in alcohol-preferring Alko Alcohol (AA) rats. Microinfusions of the long-acting and selective κ-opioid receptor antagonist JDTic (1-15μg/site) were administered bilaterally into the nucleus accumbens shell of AA rats voluntarily consuming 10% ethanol solution in the intermittent, time-restricted two-bottle choice access paradigm. JDTic (10mg/kg) was also administered subcutaneously. Both the acute and long-term effects of the treatment on ethanol intake were examined. As a reference, nor-BNI (3μg/site) was administered intra-accumbally. Systemically administered JDTic decreased ethanol intake significantly 2days and showed a similar trend 4days after administration. Furthermore, intra-accumbally administered JDTic showed a weak decreasing effect on ethanol intake long-term but had no acute effects. Intra-accumbal administration of nor-BNI tended to decrease ethanol intake. The results provide further evidence that κ-opioid receptors play a role in controlling ethanol intake and that accumbal κ-opioid receptors participate in the modulation of the reinforcing effects of ethanol. Furthermore, the results suggest that κ-opioid receptor antagonists may be a valuable adjunct in the pharmacotherapy of ethanol use disorders.