Neurochemical and behavioral effects of m-CPP in a rat model of tardive dyskinesia.

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 48 h after withdrawal from repeated (twice a day for 5 week) administration of haloperidol (at the dose of 1 mg/kg). Vacuous chewing movements (VCMs) were monitored on weekly basis. Two days after withdrawal, animals were injected with saline (1 ml/kg of body weight) or m-CPP (3 mg/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 (4 h 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.