Effects of cinanserin and p-chlorophenylalanine and their interaction with d-amphetamine on DRL performance in rats

Abstract

The effects of the serotonin antagonist cinanserin and the serotonin depletor p-chlorophenylalanine (PCPA) were compared with the effects of d-amphetamine on responding maintained by differential-reinforcement-of-low-rate schedule (DRL). d-Amphetamine (0.25–2.0 mg/kg) increased response rates and shortened interresponse times (IRTs). Cinanserin at low doses (8, 16 and 32 mg/kg) did not alter DRL responding; high doses (48 and 64 mg/kg) decreased response rates and shortened IRTs. PCPA (200 and 300 mg/kg) decreased DRL response rates and disrupted the IRT distributions for up to 72 hours post-injection, but had few effects over the subsequent 7–8 day period. d-Amphetamine given in combination with cinanserin or administered 3, 8 and 12 days post-PCPA administration resulted in decreased response rates relative to those induced by d-amphetamine alone; the d-amphetamine-induced shortening of IRTs persisted. These results suggest that cinanserin and PCPA do not exert general response-stimulant effects and that serotonergic systems are not of major functional significance in the maintenance of low rate DRL responding. These results do suggest that serotonergic systems are involved in the manifestation of the behavioral response to amphetamine, possibly as a result of a serotonergic-catecholaminergic interaction.