Effects of noradrenergic DSP4 lesion on the effectiveness of pilocarpine in reversing scopolamine-induced amnesia

We studied the effectiveness of pilocarpine in reversing the scopolamine-induced water maze learning deficit (increase in escape latencies, decrease in spatial bias) in control and DSP4- (a noradrenergic neurotoxin) lesioned rats. The water maze acquisition deficit (escape latency, first spatial bias) induced by scopolamine 0.8 mg/kg was augmented by DSP4 treatment. The water maze performance deficit induced by scopolamine was reversed by pilocarpine 4 mg/kg in both DSP4-lesioned and control rats. A smaller dose of pilocarpine (1 mg/kg) did not reverse scopolamine-induced acquisition deficit in either control or DSP4-lesioned rats. Analysis of the second spatial bias test measured 2 weeks after training revealed that pilocarpine 4 mg/kg reversed scopolamine-induced retention deficit in control and DSP4-lesioned rats. Pilocarpine 1 mg/kg reversed scopolamine-induced retention performance deficit during the second spatial bias test in control but not in DSP4-lesioned rats. The present results suggest that 1) noradrenergic and cholinergic systems may interact in the regulation of spatial acquisition and retention and 2) the effectiveness of cholinergic drugs in reversing scopolamine-induced spatial retention deficit may be affected by noradrenergic lesioning.