CHRONIC HALOPERIDOL, BUT NOT CLOZAPINE, PRODUCES ALTERED ORAL MOVEMENTS AND INCREASED EXTRACELLULAR GLUTAMATE IN RATS

Rats administered chronic haloperidol or clozapine in their drinking w ater for 6 months were monitored for changes in oral movements using a computerized video analysis system. Haloperidol-treated animals exhib ited late onset increases in small amplitude oral movements and an inc rease in the percentage of oral movements in the 1-2 Hz range, accompa nied by a decrease in oral movements in the higher frequency range(> 6 Hz) as determined by fast fourier analysis. In contrast, clozapine-tr eated rats showed a decrease in medium-sized amplitude oral movements, but did not demonstrate significant changes in the distribution of or al movements across frequencies. Extracellular concentrations of gamma -aminobutyric acid (GABA) and glutamate in the ventrolateral striatum were then assessed by intracranial microdialysis during oral drug admi nistration and 3 days after drug withdrawal. Extracellular GABA and gl utamate levels were not significantly different between groups during drug administration. However, 3 days after drug withdrawal, there was a significant increase in glutamate in the haloperidol-treated rats. N o changes were noted for glutamate levels in clozapine-treated rats or for GABA levels in either group following withdrawal. These results c onfirm the atypical profile of clozapine in an animal model of tardive dyskinesia and suggest that alterations in striatal glutamatergic fun ction follow typical, but not atypical, antipsychotic drug administrat ion.