RATS WITH PARTIAL STRIATAL DOPAMINE DEPLETIONS EXHIBIT ROBUST AND LONG-LASTING BEHAVIORAL DEFICITS IN A SIMPLE FIXED-RATIO BAR-PRESSING TASK

It is widely accepted that enduring parkinsonian symptoms are only evi dent if there are few remaining dopaminergic neurons in the substantia nigra and dopamine levels in the basal ganglia are very low [26,41]. In the present study, partial dopamine depletions were produced by inf using 6-OHDA bilaterally into the ventrolateral striatum as previously described [11,12,44]. Consistent with previous studies, behavioral de ficits were detectable in rats with partial lesions with a simple fixe d-ratio bar-pressing task. The present study demonstrated that these b ehavioral deficits were long-lasting, and that the sensitivity of this bar-pressing task could be increased by manipulating the level of dif ficulty of the task-higher fixed ratios were more sensitive to partial dopamine depletions. Deficits in rats with partial dopamine depletion s could also be detected using non-automated neurological tests of par kinsonian symptoms developed for rats with severe unilateral dopamine depletions; but these deficits were transient and not as robust as tho se detected with the bar-pressing task. Oral Sinemet (L-DOPA:carbidopa ) did not attenuate behavioral deficits related to partial dopamine de pletions in this simple fixed-ratio bar-pressing task, but the present results suggest that Parkinson's patients might be identifiable earli er in the disease process, at a time when they could benefit from trea tment with neuroprotective/neurotrophic agents. In addition, the resul ts of the present study demonstrate that robust behavioral deficits ma y emerge with age. Mild dopamine depletions that were not detectable b ehaviorally at the time of the insult became clearly evident 10 months after the lesion with this bar-pressing task, and this map represent a more clinically relevant rodent model of Parkinson's disease. (C) 19 97 Elsevier Science B.V.