title: Anxiety-like responses induced by nitric oxide within the BNST in mice: Role of CRF1 and NMDA receptors.
abstract: It has been shown that the bed nucleus of the stria terminalis (BNST) of rats contains nitrergic neurons, which are activated during animal exposure to aversive stimuli. The BNST is also populated by glutamatergic and corticotrophin releasing factor (CRFergic) neurons, which in turn are activated under stressful situations. Here we investigated the anxiogenic-like effects of intra-BNST injections of a nitric oxide (NO) donor, NOC-9 in mice. The role of CRFergic and glutamatergic systems on defensive behavior induced by NOC-9 was investigated with previous intra-BNST infusion of different doses of CP376395, a CRF type 1 receptor antagonist (CRF1), or AP-7, an NMDA (N-methyl-D-aspartate) receptor antagonist. Anxiety-like behavior was assessed immediately and 5 min after intra-BNST drug injection, exposing mice to a novel arena and to the elevated plus-maze (EPM; an anxiogenic situation). Results showed that NOC-9 provoked a short period (≈ 150 s) of freezing behavior in the novel arena and increased anxiety in the EPM. Both CP and AP-7 attenuated the anxiogenic-like effects of NOC-9 in the EPM without changing freezing behavior in the novel arena. When given alone (i.e. without prior intra-BNST injection of NOC-9), AP-7 (0.20 nmol), but not CP (0.75, 1.50, or 3.00 nmol), attenuated anxiety in mice exposed to the EPM. These results suggest that CRF1 and NMDA receptors located within the BNST differentially modulate aversive effects induced by NO production in this limbic forebrain structure.
authors.affiliation: Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos and Universidade Estadual Paulista, Araraquara, SP, Brazil; Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, 14800-903 Araraquara, SP, Brazil.
authors.forename: M P
authors.initials: MP
authors.lastname: Faria
authors.affiliation: Farmacologia, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.
authors.forename: T T
authors.initials: TT
authors.lastname: Miguel
authors.affiliation: Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, 14800-903 Araraquara, SP, Brazil.
authors.forename: K S
authors.initials: KS
authors.lastname: Gomes
authors.affiliation: Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos and Universidade Estadual Paulista, Araraquara, SP, Brazil; Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, 14800-903 Araraquara, SP, Brazil. Electronic address: souzarn@fcfar.unesp.br.
authors.forename: R L
authors.initials: RL
authors.lastname: Nunes-de-Souza
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology*; D012686:Septal Nuclei / Q000187:drug effects*; D013315:Stress, Psychological / Q000139:chemically induced / Q000378:metabolism / Q000523:psychology; D014226:Triazenes / Q000494:pharmacology; D000099052:CRF Receptor, Type 1
chemical_list: C529296:(3,6-dimethyl-2-(2,4,6-trimethylphenoxy)pyridin-4-yl)(1-ethylpropyl)amine; D000631:Aminopyridines; D018019:Receptors, Corticotropin-Releasing Hormone; D016194:Receptors, N-Methyl-D-Aspartate; D014226:Triazenes; C099612:NOC 9; D009569:Nitric Oxide; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone
keywords: Anxiety; Bed nucleus of the stria terminalis; CRF1 and NMDA receptors; Freezing; Mice; Nitric oxide