ASSESSMENT OF STRIATAL EXTRACELLULAR DOPAMINE AND DOPAMINE METABOLITES BY MICRODIALYSIS IN HALOPERIDOL-TREATED RATS EXHIBITING ORAL DYSKINESIA

Rats that had received continuous, chronic haloperidol (HAL) for 32 weeks were monitored for changes in oral movements as determined by Fast Fourier analysis of jaw movements recorded with a computerized video analysis system. Beginning at 24 weeks of administration, HAL-treated animals exhibited a pattern of significant increases in oral movement activity in the 1 to 3 Hz range and decreases in the 5 to 8 Hz range when compared to control animals. The release and metabolism of dopamine (DA) in the striatum of these animals was then assessed using intracranial microdialysis during week 32 of HAL administration and 3 days after withdrawal of HAL. Basal extracellular concentrations of the DA metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly increased in the HAL-treated rats during continuous HAL administration. Three days after withdrawal from HAL, no difference was seen in basal extracellular concentrations of any of the analytes. No difference in the magnitude of DA release was seen between groups following local application of amphetamine (10 muM) through the dialysis probe during or after chronic HAL administration. These results confirm previous findings that long-term HAL administration produces increased DA turnover during HAL administration, but that this increase does not persist following HAL withdrawal. The increased striatal DA turnover seen during chronic HAL administration may have relevance to the development of late-onset neuroleptic-induced dyskinesia in rats.