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Updated: Aug 18, 2026

Restraint to Induce Stress in Mice and Rats
Published on: December 6, 2024
[Effect of chronic variable stress on limbic corticotrapin-releasing hormone receptor]
Takuji Hishinuma1, Mikio Asakura, Hideaki Nagashima
1Department of Neuropsychiatry, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8511, Japan. jag-no8@marianna-u.ac.jp
Abstract:
The Corticotropin-releasing hormone (CRH) is a key mediator in the stress response. Two CRH-receptor subtypes have been identified in the brain, CRH-receptor 1 (CRH-R1) and CRH-receptor 2, and stress responses are mediated by the CRH-R1. In this study we have examined the effect of chronic variable stress (CVS) on the CRH-R1 immunoreactivity in the hypothalamic and limbic brain regions of the rat. For CVS we selected the six stressors described in previous reports. Male Wistar rats were randomly exposed to one stressor per a day during 13 days and finally exposed to a novel stressor (footshock). There was a significant increase of the CRH-R1 immunoreactivity 24 hours after CVS in the bed nucleus of the stria terminalis (BNST) and basolateral amygdala (BLA), whereas a single footshock had no influence on the immunoreactivity in any of the regions. A novel stressor after CVS suppressed within 24 hours the CVS-induced increase in the CRH-R1 immuoreactivity in the BNST and BLA. Our results suggest that an up-regulation of the limbic CRH-R1 may contribute to stress sensitization (vulnerability) such as an anxiety, arousal and hypersympathetic autonomic symptoms under stressful situations.
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