Role of Hypothalamic-pituitary-adrenal-axis in Affective Disorders: Anti-depressant and Anxiolytic Activity of Partial 5-HT1A Agonist in Adrenalectomised Rats

Abstract

Depression is a neurological disorder characterized by sad mood, loss of pleasure, agitation and retardation. Though most relevant neuronal pathophysiology is characterized by decrease in monoamine namely; serotonin (5‑HT), dopamine, noradrenaline level in central areas regulating mood and behavior, it inadequately explains the exact mechanism involved. Buspirone (BUS), a partial 5‑HT1A receptor agonist has shown promising anti‑depressant and anxiolytic properties in various pre‑clinical and clinical studies, but the molecular and cellular mechanisms are still unclear. Objective: The aim of this study was to investigate, in vivo, the role of hypothalamic‑pituitary‑adrenal (HPA) axis dysregulation in pathophysiology of depression‑related disorders and the anti‑depressant like activity of BUS. To simulate HPA axis dysregulation, rats were subjected to bilateral adrenalectomy (ADX). Materials and Methods: We have analyzed effect of BUS (10 mg/kg, i.p.) in ADX and sham rats using open field, sucrose consumption, elevated plus maze and hyper‑emotionality tests. Results: In all animal models tested, ADX rats exhibited significant depressive and anxiogenic states while BUS was effective in reversing the psychological diseased condition developed. Conclusion: Taken together, these data showed a prominent role of HPA axis in depression and neuronal mechanism of BUS as anti‑depressant and anxiolytic agent. Moreover, our findings suggest that BUS can be a better candidate for stress related depression and anxiety