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 [3mr/kg of body weight]. Activities in open field and light dark activity box were monitored 15 and 30 min post injection respectively. Animals 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