Dorsal striatal glucocorticoid receptor blockade prevents inhibitory avoidance memory impairment induced by restraint stress and corticosterone

Stress exposure triggers the release of corticosterone (CO), which influences learning and memory. The behavioral outcome depends on the type and duration of the stressor and the memory stage at which it is applied. Evidence suggests that CO administered before inhibitory avoidance training may hinder memory acquisition, while stress applied after training may enhance memory consolidation. This study explores the role of dorsal striatal glucocorticoid receptors (GCR) in the acquisition and subsequent retention of inhibitory avoidance memory. The first objective was to determine whether stress induced by restraint (R) or CO injection influenced acquisition and retention in the elevated T-maze (ETM). Rats were exposed to 15 min of R or received a CO injection (5 mg/kg, ip) with or without metyrapone, a glucocorticoid (GC) synthesis inhibitor. R or CO ip reduced acquisition latencies, and metyrapone administration prevented this impairment, indicating that stress disrupts memory acquisition. Next, the involvement of dorsal striatal GCR in memory was examined in ETM. The GCR antagonist mifepristone was administered directly into the dorsal striatum (DS). Under these conditions, R or CO injection failed to impair memory, suggesting that GCR activation is responsible for the deficit. Finally, CO was delivered directly into the DS. Intrastriatal CO administration produced impairments similar to those observed with R and CO injection. These findings demonstrate that GCR activation can impair memory acquisition and retention.