Single Intraperitoneal Injection of Dexamethasone Alters Stress- Related Behavior and Endogenous Glucocorticoid Signaling in Rats

Introduction: Dexamethasone induces region-specific alterations in brain monoamine metabolism, but their functional significance and relationship to glucocorticoid regulation remain unclear. Aim This study evaluated the effects of a single dexamethasone administration at 8 mg/kg on rat behavior and glucocorticoid signaling in the hippocampus, striatum, and prefrontal cortex. Method Spatial learning and memory were assessed using the Morris water maze, stress-coping behavior using the forced swim test, and locomotor and exploratory activity using the open field test. Messenger ribonucleic acid levels of the glucocorticoid receptor, Jun proto-oncogene, and Fos proto-oncogene were measured, endogenous corticosterone was determined, and potential glucocorticoid response elements were analyzed in silico . Results Dexamethasone did not impair spatial learning, memory, or general locomotor activity but increased immobility and freezing and reduced active swimming and grooming. Glucocorticoid receptor messenger ribonucleic acid remained unchanged in all brain regions. Corticosterone decreased in the striatum and prefrontal cortex but not in the hippocampus. Jun proto-oncogene and Fos proto-oncogene messenger ribonucleic acid levels increased in the hippocampus, decreased in the striatum, and remained unchanged in the prefrontal cortex. No full-length canonical glucocorticoid response elements were identified in proximal promoter regions, although half-sites, candidate glucocorticoid receptor-binding sites, and distal atypical elements were detected. Conclusion Thus, 18 h after dexamethasone administration, stress-related behavior was selectively altered while spatial learning and locomotor activity remained preserved. These effects were accompanied by region-specific changes in corticosterone and activator protein 1 components, supporting context-dependent glucocorticoid transcriptional regulation across brain regions.