Corticosterone mediates the deleterious effect of medial septal inactivation on memory retrieval.

Manipulations of hippocampal afferents, as well as exposure to glucocorticoids, impair spatial memory retrieval. Objective: We evaluated the combined effect of medial septum inactivation with muscimol (GABAA agonist) and systemic corticosterone on spatial memory retrieval. Method: Forty-one male Wistar rats were divided into four groups: Vehicle intraseptal–Vehicle intraperitoneal (Veh–Veh, n = 10), Vehicle intraseptal–Corticosterone intraperitoneal (Veh–Cort, n = 11), Muscimol intraseptal–Vehicle intraperitoneal (Mus–Veh, n = 10), and Muscimol intraseptal–Corticosterone intraperitoneal (Mus–Cort, n = 10). Animals were trained in the Barnes maze and tested for retrieval 24 hr later. Results: Animals in the groups Veh–Cort, Veh–Mus, and Mus–Cort showed deficits in the retrieval test. However, the magnitude of this deficit was smaller in the animals with the combined treatment (Mus–Cort) than in those with only muscimol (d = 0.97 for escape latency; d = 0.95 for weighted nongoal explorations). Conclusions: We reproduced the effects of muscimol and corticosterone on memory retrieval. In addition, our data showed a reduced deficit in memory retrieval after the combined treatment suggesting a role of corticosterone on the attenuation of the effect of muscimol on hippocampal synaptic activity, possible through an underlying mechanism involving glutamatergic activity on the hippocampus. We describe for the first time the relation between the activity of the septo-hippocampal system and the rapid effects of corticosterone on memory retrieval. These results suggest a therapeutic potential of compounds derived from glucocorticoids as an alternative intervention to the traditional cholinergic therapies in the alleviation of the memory impairments observed on several pathologies related to hippocampal decline. (PsycInfo Database Record (c) 2021 APA, all rights reserved)