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Study of the involvement of the nitric oxide-guanylate cyclase mechanism in the paraventricular nucleus of hypothalamus on local neuronal activation and hypothalamic-pituitary-adrenal stimulation induced by restraint stress in rats

Grant number: 12/09425-1
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): August 14, 2012
Effective date (End): February 13, 2013
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Fernando Morgan de Aguiar Correa
Grantee:Cristiane Busnardo Santiago
Supervisor: James Paul Herman
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: University of Cincinnati, United States  
Associated to the scholarship:09/05308-8 - Role of the hypothalamus paraventricular nucleus on cardiovascular and neuroendocrine responses observed during acute restraint stress in rats, BP.PD


The paraventricular nucleus of the hypothalamus (PVN) is involved in control of autonomic, neuroendocrine and behavioral responses. In previous study, we observed that PVN pretreatment with synaptic inhibitor reduced the pressor response, the fall in tail skin temperature and increase in plasma corticosterone induced by restraint stress (RS). Despite evidence of the involvement of the PVN in physiological responses to stress, the neurochemical mechanisms involved in local control of these responses by PVN are still poorly understood. Several neurotransmitters present in different subpopulations of PVN neurons have been reported to participate in the central regulation of autonomic and neuroendocrine systems; attention has been called upon the nitrergic system that appears to exert its effects by enzyme guanylate cyclase activation. Literature data have shown that nitric oxide (NO) modulates neuronal activity in other areas of the central nervous system (CNS) during stressful situations. Therefore, this project aims to study the involvement of this pathway on the activation of different neuronal subpopulations of PVN, as well as on the hypothalamic-pituitary-adrenal (HPA) stimulation, responses induced by RS. To address this issue, the present study employed c-Fos immunohistochemistry to investigate the NO-guanylate cyclase mechanism in the PVN on their local neuronal activation caused by RS and it will be evaluated this apparatus on hormone responses associated with HPA axis activation. To achieve this purpose, we will perform bilateral microinjections into the PVN with the selective neuronal NO synthase (nNOS) inhibitor NÉ-Propyl-L-arginine (N-Propyl),the NO scavenger carboxy-PTIO (C-PTIO,) or the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolol [4,3-a]quinoxalin-1-one (ODQ) before exposing rats to RS. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BUSNARDO, CRISTIANE; CRESTANI, CARLOS C.; SCOPINHO, AMERICA A.; PACKARD, BENJAMIN A.; RESSTEL, LEONARDO B. M.; CORREA, FERNANDO M. A.; HERMAN, JAMES P.. Nitrergic neurotransmission in the paraventricular nucleus of the hypothalamus modulates autonomic, neuroendocrine and behavioral responses to acute restraint stress in rats. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 90, p. 16-27, . (09/05308-8, 12/09425-1)

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