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 base line to test the therapeutic efficacy of candidate palliative, neuroprotect ive and neurorestorative drugs. Rats were subjected to unilateral 6-hydroxy dopamine (6-OHDA) lesions of striatum, medial forebrain bundle (mfb), or we re 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 b een well trained in the RDD task were sham lesioned or were given unilatera l 6-OHDA lesions of the mfb, and behavior under this baseline was studied f or more than 30 weeks. Lesions of both striatum and of mfb resulted in impa ired acquisition of RDD responding, with the relatively greater effect by t he mfb lesion. In rats previously trained under the RDD schedule, mfb lesio ns produced marked disruptions in RDD performance, which did not fully reco ver. L-DOPA administration decreased the variability of the response durati ons, primarily by decreasing the proportion of short-duration lever presses . (C) 2000 Elsevier Science B.V. All rights reserved.