Effects of serotonin (5-HT)1B receptor ligands on amphetamine-seeking behavior in rats

Background: numerous studies have indicated that serotonin (5-ht)1b receptor ligands affect the behavioral effects of psychostimulants (cocaine,amphetamine),including the reinforcing activities of these drugs. methods: to substantiate a role for those receptors in incentive motivation for amphetamine,we used the extinction/reinstatement model to examine the effects of the 5-ht1b receptor ligands on the reinstatement of extinguished amphetamine-seeking behavior. rats trained to self-administer amphetamine (0.06 mg/kg/infusion) subsequently underwent the extinction procedure. these rats were then tested for the amphetamine-primed or amphetamine-associated cue-induced reinstatement of extinguished amphetamine- seeking behavior. results: the 5-ht1b receptor antagonist sb 216641 (5-7.5 mg/kg) attenuated the amphetamine (1.5 mg/kg)- and the amphetamine- associated cue combined with the threshold dose of amphetamine (0.5 mg/kg)-induced reinstatement of amphetamineseeking behavior. the 5-ht1b receptor agonist cp 94253 (1.25-5 mg/kg) also inhibited the amphetamine-seeking behavior induced by amphetamine (1.5 mg/kg) but not by the cue combined with the threshold dose of amphetamine. the inhibitory effect of cp94253 on amphetamine-seeking behavior remained unaffected by the 5-ht1b receptor antagonist. conclusion: our results indicate that tonic activation of 5-ht1b receptors is involved in amphetamine- and cue-induced reinstatement of amphetamine-seeking behavior and that the inhibitory effects of 5-ht1b receptor antagonists on these phenomena are directly related to the motivational aspects of amphetamine abuse. the inhibitory effect of cp 94253 on amphetamine-seeking behavior seems to be unrelated to 5-ht1b receptor activation and may result from a general reduction of motivation.