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 we eks 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 w hen compared to control animals. The release and metabolism of dopamin e (DA) in the striatum of these animals was then assessed using intrac ranial microdialysis during week 32 of HAL administration and 3 days a fter withdrawal of HAL. Basal extracellular concentrations of the DA m etabolites, 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 wa s seen in basal extracellular concentrations of any of the analytes. N o difference in the magnitude of DA release was seen between groups fo llowing local application of amphetamine (10 muM) through the dialysis probe during or after chronic HAL administration. These results confi rm previous findings that long-term HAL administration produces increa sed DA turnover during HAL administration, but that this increase does not persist following HAL withdrawal. The increased striatal DA turno ver seen during chronic HAL administration may have relevance to the d evelopment of late-onset neuroleptic-induced dyskinesia in rats.