Head-Twitch Response Induced by ρ-Hydroxyamphetamine in Mice

Abstract

P-Hydroxyamphetamine (p-OHA) is an indirectly acting sympathomimetic amine which is of particularly pharmacological significance, because it is a major metabolite of amphetamine in most species examined. It is well known that amphetamine causes clinical hallucination. It is not yet clear, however, whether amphetamine or its metabolite elicites such effect. Head-twitch response (HTR) has been regarded as an experimental model for hallucination and recently we observed that p-OHA markedly induced HTR in mice. The present work was undertaken to study possible participation of a serotonergic system in the mechanism of HTR induced by p-OHA. HTR induced by intracerebroventricular (i.c.v.) injection of p-OHA continued for 20–80 min and its peak time was found to be approximately 30–40 min after the administration of p-OHA. The i.c.v. administartion of p-OHA dose-dependently induced HTR. Pretreatment with reserpine (1 mg/kg × 3, i.p.) significantly potentiated HTR induced by p-OHA. Pretreatment with serotonin (10 μg/mouse, i.c.v.) caused 2–2.5 fold increase in HTR, compared to the saline control. Pretreatment with p-chlorophenylalanine (200 mg/kg, i.p.), in contrast, reduced HTR, as did pretreatment with cyproheptadine, dimethothiazine, or morphine. These results suggest that HTR produced by p-OHA may involve the serotonergic system in the brain and this system may exert an excitatory effect on HTR.