NEUROCHEMICAL AND BEHAVIORAL EFFECTS OF M-CPP IN A RAT MODEL OF TARDIVE DYSKINESIA

Abstract

Present study was designed to monitor the responsiveness of 5HT (5-Hydroxytryptamine) -2C receptors following the long-term administration of haloperidol in rats. Effects of m-CPP (meta-Chlorophenyl piperazine) were monitored 48h after withdrawal from repeated (twice a day for 5 week) administration of haloperidol (at the dose of 1mg/kg). Vacuous chewing movements (VCMs) were monitored on weekly basis. Two days after withdrawal, animals were injected with saline (1ml/kg of body weight) or m-CPP (3mg/kg of body weight). Activities in open field and light dark activity box were monitored 15 and 30min post injection respectively. Corresponding author: E-mail: huma_biochemist@yahoo.com Pak. J. Pharm. Sci., 2007, Vol.20(3), 185-188 188Animals were then decapitated (4h post injection) to collect dorsal striatum (DS) samples for the neurochemical analysis by HPLC-EC (High Performance Liquid Chromatography with Electrochemical detection) method. Results from the present study showed significant hypolocomotive effect of m-CPP (p<0.05) in both repeated haloperidol as well as repeated saline injected rats. Neurochemical analysis of DS by HPLC-EC method showed that administration of m-CPP significantly (p<0.05) decreased 5-HIAA (5-Hydroxyindol acetic acid) in repeated haloperidol injected rats. In conclusion, present study provides evidence that 5HT-2C receptors become hypersensitive in a rat model of Tardive Dyskinesia (TD). These findings have potential implication in the treatment of TD and attenuation of EPS induced by typical neuroleptics. Keywords: Haloperidol, extra pyramidal side effects, tardive dyskinesia, m-CPP, 5HT-2C receptors.