Involvement of CRFergic neurotransmission in the lateral hypothalamus in cardiovascular and behavioral responses to stress in rats

• Grant number: 18/14284-4
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2018
• Effective date (End): August 31, 2021
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Carlos Cesar Crestani
• Grantee: Lucas Barretto de Souza
• Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Studies in humans and animals have provided evidence correlating stress with the development of various complications cardiovascular and psychiatric disorders, such as anxiety. Despite the relevance of these findings, the neurobiological mechanisms related to cardiovascular and behavioral changes evoked by stress are still poorly understood. The Lateral Hypothalamus (LH) is an important hypothalamic area that has been implicated in the integration of physiological and behavioral responses to stress. Indeed, it has been shown the involvement of HL in cardiovascular responses to stress and behavioral control. However, the local neurochemical mechanisms involved in the control of these responses by LH are still poorly understood. The CRFergic system, composed by the Corticotrophin Releasing Factor (CRF) and urucortin 1, 2 and 3, acting through activation of the CRF1 and CRF2 receptors, has been shown to be an important mechanism in the central nervous system involved in the etiology of behavioral changes and in the physiological adjustments evoked by exposure to aversive situations. Data also showed that exposure to chronic stress affects the expression of CRF receptors, besides changing the levels of CRF and urocortins in encephalic regions involved in the control of stress responses. Expression of CRF1 and CRF2 receptors, as well as CRF peptides (CRF and urucortin1 and 3) was identified within LH. Besides, microinjection of CRF into the LH evokes changes in cardiovascular and behavioral parameters. Nevertheless, a possible involvement of LH CRFergic neurotransmission in control of stress-induced cardiovascular and anxiety responses has never been investigated. Thus, our proposal in the present study is: 1) to investigate the involvement of CRFergic neurotransmission in the LH in the cardiovascular and anxiogenic responses evoked by an acute session of restraint stress in rats; 2) to evaluate the effect of previous exposure to restraint stress in the control of cardiovascular and anxiogenic responses to this stressor by the CRFergic neurotransmission in the HL of rats; 3) to investigate the involvement of CRFergic neurotransmission present in the HL in changes in baseline cardiovascular parameters and baroreflex activity, as well as in behavioral anhedonic response, induced by exposure to a chronic variable stress protocol in rats; and 4) to assess the effect of repeated exposure to restraint stress or a chronic variable stress protocol on CRF1 and CRF2 receptor protein levels in rat LH. (AU)