The effect of the GABAB agonist baclofen on cocaine self-administration in the rat was investigated. In the first experiment, rats trained to self-administer i.v. cocaine (1.5 mg/kg/inj) on a progressive ratio (PR) schedule were pretreated with various doses of baclofen (1.25, 2.5, or 5.0 mg/kg). Baclofen produced a dose-dependent decrease in the break points. In the second experiment, baclofen (2.5 mg/kg) was found to decrease significantly break points across a series of unit injection doses of cocaine (0.18, 0.37, 0.75, 1.5 mg/kg/inj). Baclofen produced only modest effects on food-reinforced responding even at the largest dose tested (5.0 mg/kg). These data suggest that baclofen may produce a specific attenuation of cocaine reinforcement. Baclofen produced no significant change in the rate of i.v. cocaine intake on a fixed ratio (FR 1) schedule. These data support a number of recent observations that rate of drug intake may be an insensitive measure of changes in the motivation to self-administer cocaine.

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 GABAB 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.

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