Neurochemical changes associated with chronic administration of typical antipsychotics and its relationship with tardive dyskinesia.

The therapeutic success of atypical antipsychotics has focused the attention on the role of receptor systems other than dopaminergic system in the pathophysiology of neuroleptic-associated extrapyramidal side effects such as tardive dyskinesia. In the present study we planned to study time-dependent changes in extracellular levels of norepinephrine, dopamine and serotonin in cortical and subcortical (including striatum) regions of brain and tried to correlate them with hyperkinetic motor activities (vacuous chewing movements [VCMs], tongue protrusions and facial jerking) in rats treated chronically with typical neuroleptics (haloperidol and chlorpromazine). Chronic administration of haloperidol (1 mg/kg) and chlorpromazine (5 mg/kg) resulted in a time-dependent increase in orofacial hyperkinetic movements. There were also significant changes in the extracellular levels of different neurotransmitters in different brain regions (cortical and subcortical regions) as measured by high-performance liquid chromatography/electrochemical detection (HPLC/ED). Both haloperidol and chlorpromazine produced time-dependent decreases in the levels of these neurotransmitters.