NEUROCHEMICAL AND BEHAVIORAL RECOVERY AFTER COLCHICINE LESIONS OF THENUCLEUS BASALIS MAGNOCELLULARIS IN RATS

Experimentally-induced lesions of the basal forebrain have been used t o test the hypothesis that the cholinergic system plays a critical rol e in learning and memory. In the present study, a basal forebrain infu sion of colchicine, a microtubule assembly inhibitor, was used to char acterize the relationship between a cholinergic marker and behavioral function. Bilateral infusions were made in the nucleus basalis magnoce llularis (NBM) of male Long-Evans rats. At 4 weeks post-lesion, behavi oral assessments were made on half of the rats in each group. These ra ts were sacrificed 1 week later and regional choline acetyltransferase (ChAT) activity was measured. The remaining rats were behaviorally te sted 11 weeks post-lesion and sacrificed 12 weeks post-lesion. The bra ins of additional rats were studied for Nissl-staining, ChAT-, GAD- an d metEnk immunoreactivity (IR) and AChE histochemistry. At 5 weeks aft er colchicine infusion, there was a significant decrease in parietal a nd frontal cortical ChAT activity, impaired acquisition of a water maz e spatial navigation task and decreased passive avoidance cross-over l atency. At 12 weeks after colchicine infusion, ChAT activity was decre ased in frontal but not parietal cortex; acquisition of the water maze task was not significantly different from vehicle-infused rats, and a significant deficit was observed in passive avoidance latency. ChAT-I R in the NBM showed a significant decrease at both time points, while changes in AChE-stained cortical fibers paralleled the ChAT activity. GAD- and metEnk-IR were decreased but were not different between the t wo time points. These data show task-specific behavioral recovery asso ciated in time with recovery of regional cholinergic markers.