title: Participation of hippocampal nitric oxide synthase and soluble guanylate cyclase in the modulation of behavioral responses elicited by the rat forced swimming test.
abstract: Systemic or hippocampal administration of nitric oxide (NO) synthase inhibitors induces antidepressant-like effects in animals, implicating increased hippocampal levels of NO in the neurobiology of depression. However, the role played by different NO synthase in this process has not been clearly defined. As stress is able to induce neuroinflammatory mechanisms and trigger the expression of inducible nitric oxide synthase (iNOS) in the brain, as well as upregulate neuronal nitric oxide synthase (nNOS) activity, the aim of the present study was to investigate the possible differential contribution of hippocampal iNOS and nNOS in the modulation of the consequences of stress elicited by the forced swimming test. Male Wistar rats received intrahippocampal injections, immediately after the pretest or 1 h before the forced swimming test, of selective inhibitors of nNOS (N-propyl-L-arginine), iNOS (1400W), or sGC (ODQ), the main pharmacological target for NO. Stress exposure increased nNOS and phospho-nNOS levels at all time points, whereas iNOS expression was increased only 24 h after the pretest. All drugs induced an antidepressant-like effect. However, whereas the nNOS inhibitor was equally effective when injected at different times, the iNOS inhibitor was more effective 24 h after the pretest. These results suggest that hippocampal nNOS and iNOS contribute to increase in NO levels in response to stress, although with a differential time course after stress exposure.
authors: aDepartment of Pharmacology, School of Medicine of Ribeirão Preto bDepartment of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto cCenter for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors: Amanda J
authors: AJ
authors: Sales
authors: Vinícius A
authors: VA
authors: Hiroaki-Sato
authors: Sâmia R L
authors: SR
authors: Joca
mesh_terms: D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000071756:Soluble Guanylyl Cyclase / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*; D013550:Swimming; D013997:Time Factors
chemical_list: C116907:1H-(1,2,4)oxadiazolo(4,3-a)-quiloxalin-1-one; D000578:Amidines; D001596:Benzylamines; C109599:N(omega)-propylarginine; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D010069:Oxadiazoles; D009569:Nitric Oxide; D001120:Arginine; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D000071756:Soluble Guanylyl Cyclase