Lateral Hypothalamus Corticotropin-releasing Hormone Receptor-1 Inhibition and Modulating Stress-induced Anxiety Behavior

Introduction: Stress is a reaction to unwanted events disturbing body homeostasis and its pathways and target areas. Stress affects the brain through the lateral hypothalamic area (LHA), the orexinergic system that mediates the effect of corticotropin-releasing hormone (CRH) through CRH Receptor Type 1 (CRHr1). Therefore, this study explores the outcome of stress exposure on anxiety development and the involvement of the LHA through LHA-CRHr1. Methods: Male Wistar rats (220-250 g) implanted with a cannula on either side of the LHA received acute or chronic stress. Subsequently, exploratory behavior was examined using the Open Field (OF), and anxiety was tested by Elevated Plus Maze (EPM). Before sacrifice, the cerebrospinal fluid (CSF) and the blood were sampled. Nissl stain was performed on fixed brain tissues. Results: Acute stress reduced exploration in of and increased anxiety in EPM. LHA-CRHr1 inhibition reversed the variables to increase the exploration and decrease anxiety. In contrast, chronic stress did not show any effect on anxiety-related behaviors. Chronic stress decreased the cell population in the LHA, which was prevented by the CRHr1 inhibition. However, the CRHr1 i