BIDIRECTIONAL MODULATION OF SCOPOLAMINE-INDUCED WORKING-MEMORY IMPAIRMENTS BY MUSCARINIC ACTIVATION OF THE MEDIAL SEPTAL AREA

The hypotheses that the medial septal area (MSA) is critical for worki ng memory and that MSA neural activity is positively regulated by chol inergic inputs leads to two testable predictions: (1) working memory c an be bidirectionally modulated by muscarinic manipulations of the MSA and (2) muscarinic activation of the MSA can enhance memory under con ditions of mnemonic impairment. Memory was assessed by T-maze spatial alternation following intraseptal infusion of muscarinic drugs in rats pretreated with intraperitoneal (IP-) injections of scopolamine. Scop olamine dose-dependently impaired working memory and shifted the hippo campal theta activity to a higher peak frequency. Intraseptal scopolam ine mimicked the behavioral effects of IP-scopolamine, and intraseptal carbachol appeared to reverse both the behavioral and physiological e ffects of IP-scopolamine. The results indicate that the amnestic effec t of antimuscarinic drugs may be due to an interaction in the MSA and that conditions of memory impairment may be alleviated by selective mu scarinic activation of the MSA. (C) 1995 Academic Press, Inc.