Exploring Corticosterone-Induced Depression Models: Mechanisms, Therapeutic Interventions, and Implications for Treatment

Corticosterone, a steroid hormone produced in the adrenal cortex, plays a crucial role in stress response and has been implicated in the pathophysiology of depression. This review synthesizes recent findings on the effects of corticosterone in various animal models of depression, highlighting its impact on behavior and neurochemical alterations. Chronic administration of corticosterone induces depressive-like symptoms in multiple species, including rodents and birds, through mechanisms involving the hypothalamic-pituitary-adrenal (HPA) axis dysregulation and the modulation of brain-derived neurotrophic factor (BDNF) levels. Pharmacological interventions such as resveratrol, curcumin, metabotropic glutamate receptor antagonists, liraglutide, and thymol have shown promise in ameliorating these symptoms by restoring neuroplasticity, regulating HPA axis function, and enhancing BDNF signaling. Additionally, studies on the consistency of corticosterone levels across species underscore the role of hormonal plasticity in behavioral outcomes and underscore complexities in hormonal regulation. The corticosterone-induced depression models offer valuable insights into potential therapeutic strategies and the biological underpinnings of depression, ultimately guiding the development of more effective treatments, particularly for disorders characterized by HPA axis dysregulation.