INTRAVENOUS COCAINE SELF-ADMINISTRATION IN MICE LACKING 5-HT1B RECEPTORS

The present experiment tested the hypothesis that 5-HT1B receptors are involved in the reinforcing effects of cocaine. Transgenic mice lacki ng 5-HT1B receptors were used as subjects and compared with wild-type mice for the acquisition and maintenance of intravenous (IV) cocaine s elf-administration. Male 129/Sv-ter and 5-HT1B-minus 129/Sv-ter inbred mice (Columbia University, New York) were initially trained to press a lever under a fixed-ratio schedule 2, first for sweetened condensed milk as reinforcer and subsequently for cocaine (2.0 mg/kg/infusion). When a stable baseline of responding was obtained, each subject was te sted under different doses of cocaine (1.0, 2.0, and 4.0 mg/kg), with the number of reinforcers per hour used as the dependent variable. Bot h strains successfully acquired food-shaping and cocaine self-administ ration but the mutant mice presented a significantly shorter latency t o meet IV cocaine self-administration acquisition criteria (p < 0.05). However, both wild-type and mutant mice had similar dose-response to cocaine. These results suggest that the 5-HT1B receptors may be implic ated in the propensity to self-administer cocaine, but other mechanism s might be involved in the maintenance of cocaine self-administration. (C) 1997 Elsevier Science Inc.