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Rats with extensive lesions of cortical cholinergic afferents as a result of infusions of 192 IgG-saporin into the basal forebrain show persistent impairments in sustained attention performance (J. McGaughy, T. Kaiser, & M. Sarter, 1996). However, the administration of neither the cholinesterase inhibitor physostigmine nor the benzodiazepine receptor partial inverse agonist FG 7142 attenuated the lesion-induced impairments in performance. The present study demonstrated that less extensive cortical cholinergic deafferentation, produced by intracortical infusions of a relatively small concentration of 192 IgG-saporin, resulted in a significant impairment in sustained attention. However, the administration of neither physostigmine (0.01–0.1 mg/kg) nor FG 7142 (0.1–1.0 mg/kg) benefited the performance of the animals. Because neither compound selectively augments performance-associated increases in acetylcholine release from residual neurons, beneficial effects on cortical cholinergic deafferentation-based impairments in attention may remain limited.