Failure of chronic physostigmine to ameliorate working memory deficits after medial septal lesions

To assess the potential usefulness of chronic acetylcholinesterase inhibition in the treatment of learning/memory disorders arising from central cholinergic deficient states, physostigmine was administered chronically to rats with medial septal lesions and the retention of a spatial/working memory task investigated. Three dose levels of physostigmine (0.025, 0.05, 0.075 mg/kg) were administered three times per day following medial septal lesions. Retention of a standard radial 8-arm maze task was assessed. Although the lesions transiently disrupted task performance, physostigmine therapy did not improve either daily performance or total recovery time. Our results suggest that chronic acetylcholinesterase inhibition is not effective in ameliorating the working memory deficits that occur after medial septal lesions.