title: Antidepressant-like effects induced by NMDA receptor blockade and NO synthesis inhibition in the ventral medial prefrontal cortex of rats exposed to the forced swim test.
abstract: BACKGROUND
  Systemic treatment with NMDA receptor (NMDAR) antagonists, inhibitors of neuronal nitric oxide synthase (nNOS) or of soluble guanylyl cyclase (sGC), induce antidepressant-like effects in rats. Increased levels of glutamate and nitric oxide (NO) in the medial prefrontal cortex (MPFC) of stressed animals have been described in the literature. However, the role of the NMDAR-nNOS-sGC pathway of the MPFC in the mediation of forced swim-induced behaviors remains unclear.
  
  
  OBJECTIVE
  The aim of this work was to test the hypothesis that the inhibition of the NMDAR-nNOS-sGC pathway in the ventral MPFC (infralimbic (IL) or prelimbic (PL)) would elicit antidepressant-like effects in the forced swim test (FST).
  
  
  METHODS
  Rats implanted with cannulae aimed at the PL or the IL were exposed to the FST and injected with LY235959 (NMDAR antagonist), NPA (nNOS inhibitor), ODQ (sGC inhibitor), or carboxy-PTIO (NO scavenger). Additional groups received the AMPA antagonist, NBQX, before the effective doses of LY235959 or NPA.
  
  
  RESULTS
  LY235959 administration into PL or IL before the FS pretest produced no effects. Administration of LY235959 (3 and 10 nmol/0.2 μL) after pretest was effective only when administered into the PL. However, the administration of NPA (0.01 nmol/0.2 μL), c-PTIO (1.0 nmol/0.2 μL), and ODQ (1.0 nmol/0.2 μL) into the PL or IL before the FST produced antidepressant-like effects. NBQX blocked the antidepressant-like effect of LY235959 but not of NPA.
  
  
  CONCLUSIONS
  Blocking NMDAR or NO signaling in the vMPFC, either in the IL or the PL, induces antidepressant-like effects in the rat FST. These effects seemingly occur through independent mechanisms, since NBQX blocked the former effect but not the latter.
authors.affiliation: Department of Pharmacology, School of Medicine, Campus USP-Ribeirão Preto, Ribeirão Preto, SP, 14049-900, Brazil.
authors.forename: Vitor Silva
authors.initials: VS
authors.lastname: Pereira
authors.affiliation: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Cafe Av, s/n, Ribeirão Preto, SP, 14040-903, Brazil.
authors.forename: Angélica
authors.initials: A
authors.lastname: Romano
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, 8240, Risskov, Denmark.|Centre of Excellence for Pharmaceutical Sciences, North West University, Potchefstroom, 2520, South Africa.
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
authors.affiliation: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Cafe Av, s/n, Ribeirão Preto, SP, 14040-903, Brazil. samia@usp.br.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, São Paulo, Brazil. samia@usp.br.
authors.forename: Sâmia R L
authors.initials: SR
authors.lastname: Joca
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D007546:Isoquinolines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D009569:Nitric Oxide; C088643:LY 235959; D052248:Nitric Oxide Synthase Type I
keywords: AMPA receptor; Antidepressant; Glutamate; NMDA receptor; Nitric oxide; Prefrontal cortex; Stress