Phencyclidine-induced head-weaving observed in mice after ritanserin treatment.

Ritanserin, a drug that blocks serotonin 5-HT2 receptors, reduced head-twitch behavior in mice caused by phencyclidine (PCP) and another serotonin-like drug, but increased head-weaving behavior. The two behaviors were inversely related. Depleting serotonin with PCPA reduced head-weaving caused by PCP plus ritanserin but not head-weaving caused by the serotonin-like drug. These results suggest PCP causes head-weaving by indirectly activating a different serotonin receptor (possibly 5-HT1) after releasing serotonin, and head-twitch by directly activating 5-HT2 receptors.

Study at a glance

Abstract

Ritanserin (0.125, 0.25, 0.5, 1.0 and 2.0 mg/kg s.c.), a selective serotonin (5-HT2) receptor antagonist, produced a dose-dependent inhibition of the head-twitch response induced in mice by phencyclidine (PCP) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). In contrast, ritanserin, dose dependently increased PCP- and 5-MeODMT-induced head-weaving. There was a significant inverse relationship between head-twitch and head-weaving responses. Pretreatment with p-chlorophenylalanine (PCPA, 300 mg/kg i.p.), a serotonin synthesis inhibitor, attenuated the head-weaving induced by the combination of PCP (12.5 mg/kg i.p.) and ritanserin but PCPA did not alter the 5-MeODMT-induced head-weaving. These results indicate that PCP induces head-weaving by interacting with a 5-HT receptor (possibly of the 5-HT1 subtype) indirectly after 5-HT release and induces head-twitch by interacting with 5-HT2 receptors directly.