Disruption of acquisition and performance of operant response-duration differentiation by unilateral nigrostriatal lesions

Response duration differentiation (RDD), an operant schedule requiring fine motor timing and control, was assessed as a possible baseline for study of the long-term consequences of nigrostriatal lesions and as a possible baseline to test the therapeutic efficacy of candidate palliative, neuroprotective and neurorestorative drugs. Rats were subjected to unilateral 6-hydroxydopamine (6-OHDA) lesions of striatum, medial forebrain bundle (mfb), or were sham lesioned, and their ability to acquire the operant task was studied in a single overnight session. In a second set of studies, rats that had been well trained in the RDD task were sham lesioned or were given unilateral 6-OHDA lesions of the mfb, and behavior under this baseline was studied for more than 30 weeks. Lesions of both striatum and of mfb resulted in impaired acquisition of RDD responding, with the relatively greater effect by the mfb lesion. In rats previously trained under the RDD schedule, mfb lesions produced marked disruptions in RDD performance, which did not fully recover. L-DOPA administration decreased the variability of the response durations, primarily by decreasing the proportion of short-duration lever presses.