COMPLEX DEFICITS ON REACTION-TIME PERFORMANCE FOLLOWING BILATERAL INTRASTRIATAL 6-OHDA INFUSION IN THE RAT

The present study examined the ability of rats subjected to bilateral 6-hydroxydopamine lesions of the terminal area of the nigrostriatal do pamine system to perform a prelearned reaction time task. This lesion model, the induction of a partial dopamine denervation of the striatum (74% depletion of dopamine striatal tissue content) with a retrograde degeneration of dopamine cell bodies in the substantia nigra, sparing the mesolimbic dopaminergic pathway, closely approximates the neurona l degeneration observed in human idiopathic Parkinson's disease. Rats were trained previously to release a lever, within a reaction time lim it, after the presentation of a visual cue through reinforcement with food pellets, The onset of the light stimulus varied randomly after an unpredictable delay period of 0.25-1.0 s, Rats with dopaminergic lesi ons showed moderate to extensive performance deficits which were not c ompensated for the five postoperative weeks. More than half of the les ioned animals (64%) showed severe deficits, characterized by a concomi tant increase in the number of anticipated (premature release of the l ever before the visual cue) and delayed responses (lever release after the reaction time limit) with shortened reaction times in some cases, A smaller proportion (36%) of lesioned animals exhibited mild impairm ent of performance with a large increase in delayed responses and leng thening of reaction times but with no change in the number of anticipa ted responses. Asymmetric lesions had no effect on the reaction time p erformance. Examination of tyrosine hydroxylase immunostaining reveale d that in the most impaired animals dopamine depletion was extensive i n the medial striatum, whereas it was restricted to the dorsolateral s triatum in the least impaired animals. Results suggest that a decrease in dopamine function at striatal level severely disrupts performance of a conditioned reaction time task. A partial dopamine depletion in t he dorsolateral striatum induces motor initiation deficits (i.e. incre ases delayed response only), Larger striatal dopamine depletion may pr oduce both motor and cognitive deficits (decrease in attentional contr ol over response output and/or disruption of stimulus-response associa tions) that could be related to similar events in Parkinson's disease.