Baclofen produces dose-related working memory impairments after intraseptal injection

Altering the activity of the septohippocampal pathway can impair spatial memory in rats. Pharmacological manipulation of septal GABA-A receptors with the agonist, muscimol, or the benzodiazepine agonist, chlordiazepoxide, also impairs spatial memory and depresses hippocampal cholinergic activity. The present experiment examined the effects of intraseptal infusion of the GABA-B agonist baclofen on the performance of rats on a working memory radial arm maze (RAM) task. Post-training administration of baclofen (3 nmol, but not 1.5 or 0.75 nmol) produced a significant impairment of RAM performance. Baclofen significantly reduced the number of correct choices and increased the number of errors committed during testing without affecting latency per arm choice or the ability of the rats to navigate the maze and consume food pellets. The data suggest that baclofen impaired retention of the task without producing proactive performance deficits. Furthermore, the present data are consistent with the hypothesis that a GABAergic mechanism in the medial septum modulates the maintenance or retrieval of spatial working memory.