Effects of cholinergic modulation on differential conditioning performance in rats were evaluated in four experiments. Animals were first trained on an operant discrimination task. In Experiment 1, performance was evaluated following different doses of physostigmine (PHY) or scopolamine (SCO). SCO impaired performance in a dose-dependent manner; doses causing moderate impairment were selected for the remainder of the study. In Experiment 2, to test effects of PHY on SCO-impaired animals, rats were tested with injections of SCO (0.125 mg/kg) plus saline, injections of SCO (0.125 mg/kg) plus PHY (0.03125 mg/kg), or two injections of saline. SCO reduced total responding, but PHY failed to attenuate the effect. Although SCO decreased performance, response patterns suggested that discrimination ability per se was unaffected. In Experiment 3, animals were given bilateral lesions of the nucleus basalis magnocellularis (NBM); performance was reassessed with or without PHY (0.03125 mg/kg) or SCO (0.125 mg/kg). Lesions alone did not affect total responding; but discrimination ability was impaired, as reflected by reduced successes and increased errors. As in Experiment 2, SCO reduced responding without affecting discrimination ability, but PHY did not improve SCO-impaired task performance. In Experiment 4, 12 months after lesions, nondrug performance of animals was reassessed. Control animals showed recovery after one session, whereas lesioned animals took four sessions to show recovery.

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I.P. Stolerman

Papers

Drug discrimination learning in rats with excitotoxic lesions of nucleus basalis and ventral globus pallidus.