PMID- 25589143
OWN - NLM
STAT- MEDLINE
DCOM- 20160202
LR  - 20220409
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 232
IP  - 13
DP  - 2015 Jul
TI  - 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.
PG  - 2263-73
LID - 10.1007/s00213-014-3853-2 [doi]
AB  - RATIONALE: 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 muL) after pretest was effective 
      only when administered into the PL. However, the administration of NPA 
      (0.01 nmol/0.2 muL), c-PTIO (1.0 nmol/0.2 muL), and ODQ (1.0 nmol/0.2 muL) into the 
      PL or IL before the FST produced antidepressant-like effects. NBQX blocked the 
      antidepressant-like effect of LY235959 but not of NPA. CONCLUSION: 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.
FAU - Pereira, Vitor Silva
AU  - Pereira VS
AD  - Department of Pharmacology, School of Medicine, Campus USP-Ribeirao Preto, 
      Ribeirao Preto, SP, 14049-900, Brazil.
FAU - Romano, Angelica
AU  - Romano A
AD  - Department of Physics and Chemistry, School of Pharmaceutical Sciences of 
      Ribeirao Preto (FCFRP), University of Sao Paulo (USP), Cafe Av, s/n, Ribeirao 
      Preto, SP, 14040-903, Brazil.
FAU - Wegener, Gregers
AU  - Wegener G
AD  - Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus 
      University, 8240, Risskov, Denmark.
AD  - Centre of Excellence for Pharmaceutical Sciences, North West University, 
      Potchefstroom, 2520, South Africa.
FAU - Joca, Samia R L
AU  - Joca SR
AD  - Department of Physics and Chemistry, School of Pharmaceutical Sciences of 
      Ribeirao Preto (FCFRP), University of Sao Paulo (USP), Cafe Av, s/n, Ribeirao 
      Preto, SP, 14040-903, Brazil. samia@usp.br.
AD  - Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), 
      University of Sao Paulo, Sao Paulo, Brazil. samia@usp.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150116
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Antidepressive Agents)
RN  - 0 (Isoquinolines)
RN  - 0 (Quinoxalines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 118876-58-7 (2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - AR2BHC0C6P (LY 235959)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/pharmacology/*therapeutic use
MH  - Depression/*drug therapy/metabolism/psychology
MH  - Dose-Response Relationship, Drug
MH  - Isoquinolines/pharmacology/therapeutic use
MH  - Male
MH  - Nitric Oxide/antagonists & inhibitors/metabolism
MH  - Nitric Oxide Synthase Type I/*antagonists & inhibitors/metabolism
MH  - Prefrontal Cortex/*drug effects/metabolism
MH  - Quinoxalines/pharmacology/therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/metabolism
MH  - *Swimming/psychology
OTO - NOTNLM
OT  - AMPA receptor
OT  - Antidepressant
OT  - Glutamate
OT  - NMDA receptor
OT  - Nitric oxide
OT  - Prefrontal cortex
OT  - Stress
EDAT- 2015/01/16 06:00
MHDA- 2016/02/03 06:00
CRDT- 2015/01/16 06:00
PHST- 2014/03/05 00:00 [received]
PHST- 2014/12/22 00:00 [accepted]
PHST- 2015/01/16 06:00 [entrez]
PHST- 2015/01/16 06:00 [pubmed]
PHST- 2016/02/03 06:00 [medline]
AID - 10.1007/s00213-014-3853-2 [pii]
AID - 10.1007/s00213-014-3853-2 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2015 Jul;232(13):2263-73. doi: 
      10.1007/s00213-014-3853-2. Epub 2015 Jan 16.