Naltrexone effects on ethanol consumption and response to ethanol conditioned cues in C57BL/6 mice

Rationale: The conditions under which naltrexone reduces ethanol consumptio n and its effect on behavior controlled by ethanol conditioned stimuli rema in unclear. Objectives: The objectives were to determine the effects of nal trexone on ethanol consumption by C57BL/6 (B6) mice when injected subcutane ously (expt 1) or delivered by osmotic minipump (expt 2), and on ethanol co nditioned cues (expt 3). Methods: Naltrexone effects on ethanol consumption and preference were measured in a continuous access two-battle choice para digm in groups of mice implanted with osmotic minipumps delivering 0-3.0 mg /kg per day or injected subcutaneously with 0-6.0 mg/kg doses. Naltrexone's (0-3.0 mg/kg) effect on ethanol-conditioned cues was indexed by its effect on the expression of ethanol place conditioning (expt 3). Results: Naltrex one produced a transient reduction in ethanol consumption and a consistent reduction in preference when injected; however, it had no effect on ethanol consumption or preference when delivered continuously by osmotic minipump. Naltrexone attenuated the expression of ethanol place conditioning in a U- shaped dose-response function. Conclusions: The transient reduction in etha nol consumption produced by injected naltrexone and the absence of an effec t when continuously delivered confirms a report that maintaining naltrexone at steady state levels may antagonize its attenuation of ethanol consumpti on. The reduced expression of ethanol place conditioning in naltrexone-inje cted mice suggests that the drug can attenuate the reinforcing effects of e thanol conditioned stimuli as was recently reported for lever responding ma intained by ethanol conditioned stimuli in rats. These effects were observe d at naltrexone doses with no readily apparent adverse side-effects, suppor ting its usefulness for treating alcoholism.