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

Author:
Zhou, Wenjie, Ye, Shandong, Luo, Rong, Wu, Li-Min, Wang, Wei
Source:
RSC advances 2019 v.9 no.16 pp. 8707-8713
ISSN:
2046-2069
Subject:
antagonists, antidepressants, blood serum, corticosterone, corticotropin, ion channels, mental depression, nervous system, rats
Abstract:
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.
Agid:
6345084