Alleviating waiting impulsivity and perseverative responding by µ-opioid receptor antagonism in two inbred mouse strains

Rationale Recent evidence has implicated the opioid system in exaggerated ethanol consumption and impulsivity deficits. The opioid receptor antagonist naltrexone (NTX) has proven efficient in reducing alcohol consumption; however, its role on impulsive behaviour is not fully characterised. Objective The aim of this study was to investigate the effects of NTX on two measures of impulsive behaviour in two inbred mouse strains that differ in ethanol preference and impulsive phenotype. Methods Two separate groups of C57BL/6J (B6, n=24) and DBA2/J (D2, n=24) male mice were exposed to intermittent ethanol (IEE; 2 g/kg) during early (PND 30–45, IEE_Early) or late (PND 45–60, IEE_Late adolescence or the respective saline control. The ability of NTX (10 mg/kg) alone, or coadministered with ethanol (0.5 g/kg), to diminish waiting impulsivity in the five-choice serial reaction time task (5-CSRTT), or improve decision-making in a mouse version of the Iowa Gambling Task (mIGT), was examined in adulthood. Results In the 5-CSRTT, NTX diminished impulsivity in both strains of mice, irrespective of previous ethanol experience. In the mIGT, NTX failed to alter risky decision-making but decreased perseverative responding. Conclusions Blocking the actions of endogenous opioidsmay attenuate waiting impulsivity, in addition to alleviating perseverative responding. In a broader context, µ-opiate antagonism may be of potential interest for impulse-control disorders.