The blockade of corticotropin-releasing factor 1 receptor attenuates anxiety-related symptoms and hypothalamus–pituitary–adrenal axis reactivity in mice with mild traumatic brain injury. Issue 2 (April 2019)

• Record Type: Journal Article
• Authors: Kosari-Nasab, Morteza; Sadeghi, Tayebeh; Bashiri, Hamideh; Shokouhi, Ghaffar; Salari, Ali-Akbar
• Is Part Of: Behavioural pharmacology. Volume 30:Issue 2/3(2019)
• Publication Date: 2019-04
• Subjects: adrenocorticotropic hormone -- corticosterone -- corticotropin-releasing factor-1 receptor -- hypothalamus–pituitary–adrenal axis -- mouse -- traumatic brain injury; Psychopharmacology -- Periodicals; Nervous System -- drug effects -- Periodicals; Behavior -- drug effects -- Periodicals; 615.78
• DOI: 10.1097/FBP.0000000000000450
• Languages: English
• ISSNs: 0955-8810

Abstract

Abstract : Recent studies have shown that mild traumatic brain injury (mTBI) is associated with higher risk for anxiety-related disorders. Dysregulation in the hypothalamus–pituitary–adrenal (HPA) axis following mTBI has been proposed to be involved in the development of neurobehavioral abnormalities; however, the underlying mechanisms are largely unknown. The aim of this study was to determine whether the corticotropin-releasing-factor-1 (CRF-1) receptor is involved in the regulation of anxiety-related symptoms in a mouse model of mTBI. Animals with or without mTBI received intracerebroventricular injections of a CRF-1 receptor agonist (CRF; 0.01 nmol/mouse) or antagonist (antalarmin; 1 µg/mouse) for 5 days, and then the animals were subjected to anxiety tests (light-dark box and zero maze). The levels of adrenocorticotropic hormone and corticosterone, the most important markers of HPA axis, were also measured after behavioral tests. Our results indicated that mTBI-induced anxiety-related symptoms in mice through increased levels of adrenocorticotropic hormone and corticosterone, showing HPA axis hyperactivity. Interestingly, activation of CRF receptor by a subthreshold dose of CRF resulted in significant increases in anxiety-like behaviors and HPA axis response to stress, whereas blockade of CRF receptors by a subthreshold dose of antalarmin decreased anxiety-related symptoms and HPA axis response to stress in mTBI-induced mice. Collectively, these findings suggest that the CRF-1 receptor plays an important role in the regulation of anxiety-related behaviors following mTBI induction in mice and support the hypothesis that blockade of the CRF-1 receptor may be a promising therapeutic target for anxiety-related disorders in patients with TBI.