Inhibition of acid-sensing ion channels reduces the hypothalamus-pituitary-adrenal axis activity and ameliorates depression-like behavior in rats

• Published in: RSC advances Vol. 9; no. 16; pp. 877 - 8713
• Main Authors: Zhou, Wenjie, Ye, Shandong, Luo, Rong, Wu, Li-Min, Wang, Wei
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 15.03.2019; The Royal Society of Chemistry
• Subjects: antagonists; Antidepressants; blood serum; Chemistry; corticosterone; corticotropin; Elevation; Hypothalamus; Ion channels; Mental depression; Nervous system; rats; Signs and symptoms
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/c9ra00020h

Depression is the leading cause of disability worldwide, and its treatment represents a major clinical challenge. The hypothalamus-pituitary-adrenal (HPA) axis has been known to play a crucial role in depression and serves as a target for antidepressants. Acid-sensing ion channels (ASICs) are widely expressed in the nervous system and may be implicated in depression. Whether ASICs could act on the HPA axis to affect depression-related behaviors is not fully understood. In this study, we investigated the effect of inhibition of ASICs on the HPA axis activity in chronic stress-subjected rats. We found that treatment with the ASIC selective antagonist amiloride reversed chronic stress-induced elevation of adrenocorticotropic hormone (ACTH) and corticosterone in serum, which is reflective of the HPA axis activity. In addition, amiloride also alleviated chronic stress-induced anhedonia-like behavior. These results suggest that inhibition of ASICs may act on the HPA axis to alleviate the symptoms of depression. Depression is the leading cause of disability worldwide, and its treatment represents a major clinical challenge.