Antagonism of GABAergic transmission within the septum disrupts working/episodic memory in the rat

Male Sprague-Dawley rats, trained to perform a standard or delayed-non-match-to-sample radial arm maze task, were implanted with a single cannula aimed at the medial septal nucleus. A within-subjects design was utilized to examine the effects of intraseptal administration of the GABAergic antagonist bicuculline on performance of these tasks. Bicuculline (0-0.5 microgram/0.5 microliter) infusion produced dose-dependent impairments when administered prior to performance of a standard radial arm maze task. Post-training infusion of bicuculline (0.-0.25 microgram/0.5 microliter) also induced dose-dependent impairments in the delayed version (4 h) of the task. Further testing indicated that post-training administration of a low dose of bicuculline (0.05 microgram) in the delayed version of the task induced a deficit at a 4-h, but not a 1-h, retention interval. The latter indicates that the impairment varied as a function of bicuculline dose and increasing task difficulty (longer retention intervals). Previous observations indicated that post-training administration of the GABAergic agonist muscimol and the antagonist bicuculline could induce deficits in the performance of the delayed task. The present findings demonstrate that intraseptal bicuculline treatment can disrupt ongoing radial maze performance, as well as the maintenance and/or retrieval of memories necessary for performance of the delayed version of the task. These findings suggest that either activation or blockade of intraseptal GABA receptors is sufficient to disrupt working/episodic memory processes. The role of septum and septohippocampal pathway in working/episodic memory is discussed.