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-Evans rats of the muscarinic antagonists scopolamine (0.0125, 0.05, 0.2 and 0.8mg/kg s.c.), the M(1) antagonist pirenzepine, the M(2) antagonist AF-DX 116, the M(3) antagonist UH-AH 37 (each 3.2, 10, 32µg/rat, i.c.v.), and the cholinergic depleting agent, hemicholinium-3 (0.04, 0.2, 1.0 and 5.0µg/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 32µg, suggesting that antagonism of both M(3) and other muscarinic receptors (including M(1)) had a greater effect on performance than selective antagonism of the M(1) or M(2) receptors. These data indicate that the disruptive effects of cholinergic antagonism on attentionally demanding tasks are strengthened by activity at multiple subtypes of the receptor.