Baclofen suppression of cocaine self-administration: demonstration using a discrete trials procedure

Abstract

 We have previously reported that rats display a circadian pattern of cocaine self-administration if access to drug is limited to 10-min discrete trials that are separated by at least 20 min. In the present study, the pattern of cocaine intake (1.5 mg/kg per injection) was studied in two large groups of animals that were maintained on different 12-h light/dark cycles (3 a.m. to 3 p.m. versus 10 a.m. to 10 p.m.). Regardless of the time of light onset, a circadian pattern of cocaine self-administration was observed. Maximum cocaine intake occurred during the final 6 h of the dark period and was followed by a relative abstinence period during the light phase. This highly predictable pattern of drug taking behavior provided an opportunity to explore the effect of baclofen, a GABA_B agonist, on the initiation of self-administration behavior. In two separate studies, acute treatment with baclofen (1.25–5.0 mg/kg) was shown to suppress cocaine intake for at least 4 h. Baclofen had no significant effect on responding for food reinforcement. Previous results have indicated that baclofen appears to reduce specifically the motivation to respond for cocaine. Together, these data suggest that baclofen should be considered as a possible pharmacotherapeutic agent in cocaine addiction.