Effects of selective antagonism or depletion of the cholinergic system on visual discrimination performance in rats.

A two-lever simultaneous visual discrimination task was used to study the effects on performance in Long-Kvans rats of the muscarinic antagonists scopolamine (0.0125, 0.05, 0.2 and 0.8 mg/kg s.c), the M1 antagonist pirenzepine, the M2 antagonist AF-DX 116, the M3 antagonist UH-AH 37 (each 3.2, 10, 32 μg/rat, i.c.v.) and the cholinergic depleting agent, hemicholinium-3 (0.04, 0.2, 1.0 and 5.0 μg/rat i.c.v.). Scopolamine dose-dependently decreased accuracy, increased the number of trials on which the rats failed to respond, and significantly lengthened latency to respond. Only the highest doses of hemicholinium-3, pirenzepine and AF-DX 116 reduced accuracy and increased errors of omission as well as response latency, UH-AH 37 reduced overall task performance at 10 and 32 μg, suggesting that antagonism of both M3 and other muscarinic receptors (including M1) had a greater effect on performance than selective antagonism of the M1 or M2 receptors. These data indicate that the disruptive effects of cholinergic antagonism on atteniionally demanding tasks are strengthened by activity at multiple subtypes of the receptor.