Effect of 5-HT2c Receptor Modulation on the m-Chlorophenlpiperazine-Induced Hypoactivity / 대한정신약물학회지

ABSTRACT

It was aimed to investigate the effect of 5-HT2C receptor modulation on the rat behavioral responses induced by 1-(m-chlorophenyl) piperazine(mCPP), a major metabolite of trazodone. The animal activities(ambulation, stereotypy and total activity) were measured for 3 hours following mCPP administration, using an animal activity meter which accumulates the frequency of light beam interruption. mCPP(1-10 mg / kg, i.p.) induced dose-dependent decreases in ambulation and stereotypy, consequently leading to hypoactivity. The hypoactivity induced by mCPP(1mg / kg, i.p.) was significantly inhibited by pretreatment with mianserin(1mg / kg, i.p.), an antagonist with high affinity for 5-HT2C receptor, whereas pretreatment with 5-HT2 antagonists, ketanserin and ritanserin(1mg / kg, i.p., respectively) was without effect. Furthermore, long-term pretreatment with imipramine(10mg / kg, i.p., b.i.d. for 2 weeks) markedly attenuated the mCPP-induced hypoactivity. Mianserin and imipramine in the absence of mCPP did not increase the animal activity. Taken together, these results indicate that the mCPP-induced hypoactivity is mediated by 5-HT2C receptor, and that selective 5-HT2C antagonists and down regulation of 5-HT2C receptor might be useful for inhibiting the mCPP-induced hypoactivity.