ACUTE CORTICOSTERONE ADMINISTRATION INDUCES DEPRESSION-LIKE BEHAVIORS THROUGH DOPAMINE DEPLETION IN THE NUCLEUS ACCUMBENS

Acute elevations in stress hormones can rapidly influence neural function, but it remains unclear whether a single exposure to corticosterone is sufficient to induce depression-like behaviors through alterations in mesolimbic dopamine circuitry. While chronic corticosterone models have been extensively studied, the early neural events triggered by acute glucocorticoid signaling—particularly within the ventral tegmental area (VTA)–nucleus accumbens (NAc) pathway—are poorly defined. In this study, we examined whether acute corticosterone administration elicits depressive phenotypes through dopamine-related mechanisms. Mice received a single corticosterone injection, and depression-like behaviors were assessed 24 hours later using the forced swim test (FST) and tail suspension test (TST). Neuronal activity changes were evaluated by c-Fos immunohistochemistry in the VTA and NAc, with additional quantification of GABAergic neuron activation within the VTA. Planned biochemical and electrophysiological analyses, including dopamine ELISA and local field potential (LFP) recordings in the NAc, were incorporated to characterize dopamine depletion and circuit-level alterations. Acute corticosterone significantly increased immobility in both behavioral assays, indicating rapid and robust depression-like behaviors. Immunohistochemical analyses revealed increased c-Fos expression in VTA GABAergic neurons and decreased c-Fos expression in the NAc, suggesting suppressed mesolimbic dopamine output. These findings indicate that acute corticosterone rapidly shifts the excitatory–inhibitory balance within the VTA–NAc pathway toward reduced dopaminergic signaling. Our results demonstrate that a single corticosterone exposure is sufficient to induce depression-like behaviors through activation of VTA GABAergic neurons and subsequent suppression of NAc neuronal activity, revealing an underappreciated mechanism by which acute glucocorticoid surges disrupt mesolimbic dopamine circuitry.