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

BackgroundNumerous 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.MethodsTo substantiate a role for those receptors in incentive motivation for amphetamine, we used the extinction/reinstatement model to examine the effects of the 5-HT_1b 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.ResultsThe 5-HT_1b 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-HT_1b 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-HT_1b receptor antagonist.ConclusionOur results indicate that tonic activation of 5-HT_1b receptors is involved in amphetamine- and cue-induced reinstatement of amphetamine-seeking behavior and that the inhibitory effects of 5-HT_1b 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-HT_1b receptor activation and may result from a general reduction of motivation.