Acamprosate attenuates cocaine- and cue-induced reinstatement of cocaine-seeking behavior in rats

Abstract

Rationale: Acamprosate (calcium acetylhomotaurinate) is a glutamatergic neuromodulator used for the treatment of alcoholism, but its potential efficacy in the treatment of psychostimulant addiction has not been explored.

Objectives: The purpose of this study was to assess the effects of acamprosate on cocaine-stimulated locomotor activity, cocaine self-administration, and cue- and cocaine-induced reinstatement of cocaine-seeking behavior.

Materials and methods: All experiments utilized once-daily treatment for 5 consecutive days. First, the effects of saline or acamprosate (100, 300, or 500 mg/kg intraperitoneally) on body weight were examined. On the last day of treatment, locomotor activity was assessed before and after drug treatment, after which all animals received an acute challenge of cocaine (10 mg/kg). Next, a separate group of rats were trained to intravenously (IV) self-administer cocaine (0.6 mg/kg per infusion), subjected to extinction procedures, and then tested for effects of acamprosate on cue- or cocaine-induced reinstatement. A third group of rats was trained to self-administer cocaine as described above and were treated with saline or acamprosate before daily IV self-administration sessions.

Results: Repeated administration of 500 mg/kg acamprosate but not lower doses produced reductions in both body weight and spontaneous locomotor activity, and thus this dose was not tested further. Acamprosate at 300 mg/kg but not 100 mg/kg attenuated both cocaine- and cue-induced reinstatement without altering baseline patterns of cocaine self-administration or cocaine-stimulated hyperlocomotion.

Conclusions: Acamprosate attenuates both drug- and cue-induced reinstatement of cocaine-seeking behavior, suggesting that this compound may serve as a potential treatment for preventing relapse in cocaine-addicted humans.