The κ-opioid receptor antagonist JDTic decreases ethanol intake in alcohol-preferring AA rats
RATIONALE: 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.
OBJECTIVES: 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.
METHODS: Microinfusions of the long-acting and selective κ-opioid receptor antagonist JDTic (1-15 μg/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 (10 mg/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 (3 μg/site) was administered intra-accumbally.
RESULTS: Systemically administered JDTic decreased ethanol intake significantly 2 days and showed a similar trend 4 days 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.
CONCLUSIONS: 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.
Uhari-Vaananen, J., Raasmaja, A., Backstrom, P., Oinio, V., Carroll, F. I., Airavaara, M., ... Piepponen, P. (2018). The κ-opioid receptor antagonist JDTic decreases ethanol intake in alcohol-preferring AA rats. Psychopharmacology, 235(5), 1581-1591. DOI: 10.1007/s00213-018-4868-x