Intravenous cocaine self-administration in mice lacking 5-HT1B receptors

Pharmacol Biochem Behav. 1997 Jul;57(3):407-12. doi: 10.1016/s0091-3057(96)00444-3.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cocaine / pharmacology*
  • Conditioning, Operant / drug effects*
  • Dose-Response Relationship, Drug
  • Injections, Intravenous
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Serotonin / drug effects*
  • Reinforcement, Psychology
  • Self Administration*


  • Receptors, Serotonin
  • Cocaine