Lateral Hypothalamus Corticotropin Releasing Hormone Receptor-1 Inhibition Modulates Stress- Induced Anxiety Behavior

Abstract

Stress is a reaction to unwanted events disturbing body homeostasis which influences its pathways and target areas. Stress affects the brain through the lateral hypothalamic area (LHA) 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. Male Wistar rats (220-250g) implanted with a cannula in either side of the LHA received acute or chronic stress. Subsequently, exploratory behavior and anxiety was examined using the open field (OF) and elevated plus maze (EPM), respectively. Prior to sacrifice, the cerebrospinal fluid (CSF) and the blood were sampled. Nissl stain was performed on fixed brain tissues. Acute stress resulted in a decrease of exploration in the OF and an increase of anxiety in the EPM. LHA-CRHr1 inhibition reversed the variables to increase the exploration and decrease the anxiety. In contrast, chronic stress did not show any effect on the anxiety-related behaviors. Chronic stress decreased the cell population in the LHA, which was prevented by the CRHr1 inhibition. However, the CRHr1 inhibition was unable to reverse the chronic stress increase of the CSF orexin level. Furthermore, both acute and chronic stresses increased the plasma corticosterone level and only the CRHr1 inhibition impeded the effect. Our results recognize LHA-CRHr1 as a capable candidate modulating acute stress-induced anxiety development and chronic stress-induced changes in the cellular population of the region.