The effects of serotonergic disruption on the locomotor response induced by cocaine, phencyclidine, and a phencyclidine analog

Abstract

This study assessed the involvement of serotonergic systems in the locomotor-stimulating effects of cocaine, phencyclidine (PCP), and the PCP analog, N- (1-(2-benzo(b)thiophenyl)cyclohexyl) piperidine (BTCP). Central serotonin (5-HT) activity was disrupted in rats with para-chloroamphetamine (p-CA), or ritanserin pretreatment, and by lesioning of the medial raphe (MR) and dorsal raphe (DR) nuclei. P-CA potentiated cocaine- and PCP- but not BTCP-induced hyperactivity. Ritanserin enhanced PCP hyperlocomotion and attenuated caffeine hyperactivity, but failed to alter cocaine and BTCP hyperlocomotion. MR lesions, but not DR lesions, dramatically increased spontaneous activity and potentiated the hyperlocomotion of cocaine, BTCP, and caffeine but not of PCP. This differential sensitivity to 5-HT disruption may reflect the relative importance of 5-HT systems in mediating the dopamine-dependent actions of these drugs. These results are discussed in relation to the neurochemical bases of drug reinforcement and schizophrenia.