Dopamine and Serotonin Metabolism in the Dorsal and Ventral Striatum of Haloperidol-induced Tardive Dyskinesia Model in Rats

The main candidate brain regions for abnormalities in schizophrenia have been striatum, frontal cortex and amygdala. Typical antipsychotics exert their effects via their actions in striatum. It is suggested that treatment with haloperidol consistently induce 70-80 % occupancy of the striatal D2 receptors. A serious side effect of long term use of traditional neuroleptic is the precipitation of tardive dyskinesia (TD). Long term administration of haloperidol produces vacuous chewing movements (VCMs) in rats. VCMs in animals following long term use of haloperidol is often taken as a model of tardive dyskinesia. Previous studies from our laboratory showed that long term administration of haloperidol increases the responsiveness of pre- and postsynaptic 5-hydroxytryptamine (5-HT; serotonin) -1A receptors. Therefore, the present study was aimed to monitor the metabolism of dopamine (DA) and serotonin (5-HT) in the dorsal striatum and ventral striatum of rats exhibiting TD. The results showed that repeated administration and withdrawal from haloperidol increases dopamine metabolism in both dorsal and ventral striatum. The levels of dopamine but not their metabolites were smaller in dorsal striatum of rats repeatedly injected with haloperidol. 5-HT metabolism increases in the dorsal striatum following withdrawal from haloperidol. The results suggest that increase in 5-HT metabolism particularly in dorsal striatum is involved in the inhibition of VCMs following haloperidol withdrawal in rats.