Stimulation of serotonin1B receptors induces conditioned place aversion and facilitates cocaine place conditioning in rats

Rationale: Changes in serotonin(1B) (5-HT1B) receptor function appear to modify the reinforcing properties of cocaine, but the direction of this effect is not completely clear. Pharmacological stimulation of 5-HT1B enhanced the rewarding properties of self-administered cocaine while attenuating the threshold-reducing effect of cocaine in the intracerebral brain stimulation procedure. Objective: The present study investigates how pharmacological modification of 5-HT1B receptor-mediated neurotransmission influence cocaine motivational properties in the conditioned place preference paradigm in rats. Methods: In separate groups of rats the motivational properties of CP 94,253, a selective 5-HT1B agonist, or GR 127935, a 5-HT1B/D receptor partial agonist, given alone or in combination, were determined. To evaluate their influence on cocaine-induced place conditioning, CP 94,253, that was found to be aversive, was given every day before each conditioning session, while GR 127935, which given alone had no effect, was administered only before cocaine conditioning, sessions. Results: CP 94,253, injected IP at 2.5 and 10 (but not 0.5) mg/kg produced place aversion in the place conditioning paradigm. The aversive effect of 2.5 mg/kg CP 94,2253 was completely reversed by 10 mg/kg SC GR 127935. Given before every conditioning session, CP 94,253 did not modify place conditioning by four injections of 10 mg/kg cocaine but at 2.5 mg/kg it potentiated a sub-threshold dose of cocaine. The place preference caused by these two drugs was completely reversed by 10 mg/kg GR 127935. The antagonism by GR 127935 of CP 94,253's effects was shown not to be due to the induction of state-dependent effects. Conclusion: The results suggest that stimulation of 5-HT1B receptors causes place aversion, and enhances the effect of low doses of cocaine in the conditioned place preference paradigm.