Membrane-initiated glucocorticoid signaling in the dorsomedial striatum modulates resistance to extinction.

Corticosterone (CORT) modulates aversive memory through glucocorticoid receptor signaling. Although classical models emphasize intracellular receptors and transcriptional mechanisms, glucocorticoids can also produce rapid, non-genomic effects through membrane-associated signaling. The dorsomedial striatum (DMS) is critical for goal-directed learning, but its contribution to the extinction of aversive memory remains unclear. Here, we investigated whether membrane-associated glucocorticoid signaling in the DMS modulates inhibitory avoidance (IA) consolidation and extinction as a function of learning strength. Immediately after IA training, rats received bilateral intra-DMS infusions of corticosterone conjugated to bovine serum albumin (CORT-BSA), a membrane-impermeable ligand commonly used to activate membrane-associated glucocorticoid signaling. In a dose-response experiment, post-training intra-DMS CORT-BSA enhanced IA retention, with maximal efficacy at an intermediate dose, consistent with an inverted-U function. Using this effective dose, we then examined extinction across training intensities. CORT-BSA increased resistance to extinction after low-intensity training (0.5 mA), produced a transient effect after moderate training (1.0 mA), and facilitated extinction after intense training (3.0 mA). These findings suggest that rapid membrane-associated glucocorticoid signaling in the DMS modulates the persistence of aversive memory as a function of learning strength, extending current models of striatal involvement in extinction.