BACLOFEN PRODUCES DOSE-RELATED WORKING-MEMORY IMPAIRMENTS AFTER INTRASEPTAL INJECTION

Altering the activity of the septohippocampal pathway can impair spati al memory in rats. Pharmacological manipulation of septal GABA-A recep tors with the agonist, muscimol, or the benzodiazepine agonist, chlord iazepoxide, also impairs spatial memory and depresses hippocampal chol inergic activity. The present experiment examined the effects of intra septal infusion of the GABA-B agonist baclofen on the performance of r ats on a working memory radial arm maze (RAM) task. Post-training admi nistration of baclofen (3 nmol, but not 1.5 or 0.75 nmol) produced a s ignificant impairment of RAM performance. Baclofen significantly reduc ed the number of correct choices and increased the number of errors co mmitted during testing without affecting latency per arm choice or the ability of the rats to navigate the maze and consume food pellets. Th e data suggest that baclofen impaired retention of the task without pr oducing proactive performance deficits. Furthermore, the present data are consistent with the hypothesis that a GABAergic mechanism in the m edial septum modulates the maintenance or retrieval of spatial working memory. (C) 1994 Academic Press, Inc.