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Study of the involvement of hippocampal nNOS/sGC pathway on stress-induced behavioral consequences.

Grant number: 09/00323-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2009
Effective date (End): October 31, 2011
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal researcher:Sâmia Regiane Lourenço Joca
Grantee:Amanda Juliana Sales
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:07/03685-3 - Typical and atypical neurotransmitters in neuropsychiatric disorders, AP.TEM

Abstract

Recent evidences have suggested that nitric oxide (NO) might be involved on the neurobiology of depression, since the its synthesis inhibition induces antidepressant-like effects in animal models. The participation of specific brain regions and the molecular mechanisms involved in such effects remain to be investigated. Considering that intra-hippocampal injection of a preferential inhibitor of neuronal NO synthase (nNOS) induces antidepressant-like effects in rats, it is believed that increased hippocampal levels of NO in response to stress exposure might trigger the development of depressive-like behaviors, such as the increased immobility at the forced swimming test (FST). However, the participation of local cGMP formation through the activation of sGC, the principal target for NO, has not been studied so far. Therefore, the aim of the present study is to investigate the involvement of nNOS-sGC pathway in the modulation of the depressive-like behavior in the FST. For this purpose, male Wistar rats with guide cannulas aimed at the dorsal hippocampus will be submitted to a forced swimming pretest (PT, 15 min) and, immediately after, they will receive an intra-hippocampal injection of Nw-propil-L-aginina (selective nNOS inhibitor: 0.01, 0.1 or 1.0 nmol/0.5uL), c-PTio (NO scavenger: 0.1, 1.0, 3 or 10 nmol/0.5uL), ODQ (sGC inhibitor: 1, 10 ou 100 nmol/0.5¼L) or vehicle (0.5uL). Twenty four hours later, the animals will be submitted to a forced swimming test (5min), when the total immobility time will be recorded (antidepressants reduce it).