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 lacking 5-HT1B receptors were used as subjects and compared with wild-type mice for the acquisition and maintenance of intravenous (IV) cocaine self-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 tested 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. Both strains successfully acquired food-shaping and cocaine self-administration, but the mutant mice presented a significantly shorter latency to 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 implicated in the propensity to self-administer cocaine, but other mechanisms might be involved in the maintenance of cocaine self-administration.