CORRELATION OF APOMORPHINE-INDUCED AND AMPHETAMINE-INDUCED TURNING WITH NIGROSTRIATAL DOPAMINE CONTENT IN UNILATERAL 6-HYDROXYDOPAMINE LESIONED RATS

In the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of Par kinson's disease, controversy exists concerning the use of apomorphine -or D-amphetamine-induced rotations as reliable indicators of nigrostr iatal dopamine depletion. Our objective was to evaluate which, if eith er, drug-induced behavior is more predictive of the extent of nigrostr iatal dopamine depletion. Fischer 344 and Sprague-Dawley rats were uni laterally injected with 9mug/4mul/4 min 6-hydroxydopamine into the med ial forebrain bundle. The animals were behaviorally tested with apomor phine (0.05 mg/kg, s.c.) and D-amphetamine (5.0 mg/kg, s.c.). Followin g testing, the brains were removed and the right and left striata, sub stantia nigra and ventral tegmental area were dissected free and quick ly frozen at -70-degrees-C for analysis of catecholamine content by hi gh performance liquid chromatography coupled with electrochemical dete ction. Our results indicate that an animal which has greater than a 90 % depletion of dopamine in the striatum might not rotate substantially on apomorphine, without a concomitant depletion of > 50% of the DA co ntent in the corresponding substantia nigra. No correlations were seen involving depletions of the ventral tegmental area and the extent of the lesions to the striatum. Submaximally lesioned (75-90% depleted) r ats were found to rotate on D-amphetamine but not on apomorphine. In a ddition, control rats that did not receive lesions were often seen to rotate extensively on D-amphetamine. We therefore conclude that maxima l lesions of the striatum and substantia nigra are required to generat e rotations demonstrable with low dose apomorphine but not with D-amph etamine. Apomorphine, rather than D-amphetamine, is thus a better pred ictor of maximal lesions of the striatum produced by 6-OHDA.