The monoamine stabilizer (-)-OSU6162 prevents the alcohol deprivation effect and improves motor impulsive behavior in rats.

Abstract

Alcohol craving, in combination with impaired impulse control, often leads to relapse. The dopamine system mediates the rewarding properties of alcohol but is also involved in regulating impulsive behavior. The monoamine stabilizer (−)‐OSU6162 (OSU6162) has the ability to stabilize dopamine activity depending on the prevailing dopaminergic tone and may therefore normalize the dopaminergic transmission regulating both alcohol use disorder and impulsivity. We have recently showed that OSU6162 attenuates voluntary alcohol consumption, operant alcohol self‐administration, alcohol withdrawal symptoms and cue‐induced reinstatement of alcohol seeking in rats. Here, we evaluated OSU6162's effects on motor impulsivity in Wistar rats that had voluntarily consumed alcohol or water for 10 weeks. The five‐choice serial reaction time task was used to measure motor impulsivity, and a prolonged waiting period (changed from 5 to 7 seconds) was applied to induce premature responses. OSU6162‐testing was conducted twice a week (Tuesdays and Fridays), every other week with regular baseline training sessions in between. We also tested OSU6162's effects on the alcohol deprivation effect in long‐term alcohol drinking Wistar rats. The results showed that OSU6162 (30 mg/kg) pre‐treatment significantly improved motor impulsivity in the five‐choice serial reaction time task in both alcohol and alcohol‐naïve rats. Moreover, OSU6162 (30 mg/kg) pre‐treatment prevented the alcohol deprivation effect, i.e. relapse‐like drinking behavior after a forced period of abstinence in long‐term drinking rats. In conclusion, our results provide further support for OSU6162 as a novel treatment for alcohol use disorder. The results further indicate that improvement of motor impulse control might be one mechanism behind OSU6162's ability to attenuate alcohol‐mediated behaviors.