Disulfiram facilitates the development and expression of locomotor sensitization to cocaine in rats

Background Disulfiram (DS; Antabuse) inhibits dopamine-β-hydroxylase leading to increased brain dopamine levels and shows treatment efficacy for cocaine addiction. Yet few preclinical studies have been performed. This study establishes the effects of DS on locomotor sensitization to cocaine in rats. Methods Rats were administered vehicle, cocaine (10 mg/kg; intraperitoneally [IP]), or DS (50 or 100 mg/kg; IP) alone or in combination for 5 days (development phase). Locomotor activity was measured for 60-min each day. After a 10-day drug washout, rats were administered cocaine, and locomotor activity was measured (expression phase). Plasma cocaine levels were assessed in separate groups of rats administered one of two cocaine doses (0 or 10 mg/kg) and one of two DS doses (0 or 100 mg/kg) for 5 days. Ten days later, blood was collected 60-min postcocaine injection. Results The development of cocaine locomotor sensitization was facilitated by DS even though DS alone had minimal effect on activity levels. Furthermore, expression of sensitization was greatest in rats previously administered DS, an effect that cannot be attributed to altered plasma cocaine levels. Conclusions Because DS shows treatment efficacy for cocaine addiction, results from this study suggest potential treatment agents should enhance, not attenuate, locomotor sensitization in rats.