PMID- 30890202
OWN - NLM
STAT- MEDLINE
DCOM- 20200114
LR  - 20211204
IS  - 1601-5215 (Electronic)
IS  - 0924-2708 (Linking)
VI  - 31
IP  - 3
DP  - 2019 Jun
TI  - Prelimbic neuronal nitric oxide synthase inhibition exerts antidepressant-like 
      effects independently of BDNF signalling cascades.
PG  - 143-150
LID - 10.1017/neu.2018.39 [doi]
AB  - OBJECTIVES: NMDA antagonists and nitric oxide synthase (NOS) inhibitors induce 
      antidepressant-like effects and may represent treatment options for depression. 
      The behavioural effects of NMDA antagonists seem to depend on Tyrosine kinase B 
      receptor (TrkB) activation by BDNF and on mechanistic target of rapamycin (mTOR), 
      in the medial prefrontal cortex (mPFC). However, it is unknown whether similar 
      mechanisms are involved in the behavioural effects of NOS inhibitors. Therefore, 
      this work aimed at determining the role of TrkB and mTOR signalling in the 
      prelimbic area of the ventral mPFC (vmPFC-PL) in the antidepressant-like effect 
      of NOS inhibitors. METHODS: Pharmacological treatment with LY235959 or ketamine 
      (NMDA antagonists), NPA or 7-NI (NOS inhibitors), BDNF, K252a (Trk antagonist) 
      and rapamycin (mTOR inhibitor) injected systemically or into vmPFC-PL followed by 
      behavioural assessment. RESULTS: We found that bilateral injection of BDNF into 
      the vmPFC-PL induced an antidepressant-like effect, which was blocked by 
      pretreatment with K252a and rapamycin. Microinjection of LY 235959 into the 
      vmPFC-PL induced antidepressant-like effect that was suppressed by local 
      rapamycin but not by K252a pretreatment. Microinjection of NPA induced an 
      antidepressant-like effect insensitive to both K252a and rapamycin. Similarly, 
      the antidepressant-like effects of a systemic injection of ketamine or 7-NI were 
      not affected by blockade of mTOR or Trk receptors in the vmPFC-PL. CONCLUSION: 
      Our data support the hypothesis that NMDA blockade induces an antidepressant-like 
      effect that requires mTOR but not Trk signalling into the vmPFC-PL. The 
      antidepressant-like effect induced by local NOS inhibition is independent on both 
      Trk and mTOR signalling in the vmPFC-PL.
FAU - Pereira, Vitor Silva
AU  - Pereira VS
AUID- ORCID: 0000-0002-9051-3154
AD  - 1Translational Neuropsychiatry Unit,Department of Clinical Medicine,Aarhus 
      University,8240 Risskov,Denmark.
FAU - Suavinha, Angelica C D Romano
AU  - Suavinha ACDR
AD  - 3Department of Physics and Chemistry,School of Pharmaceutical Sciences of 
      Ribeirao Preto,Campus USP-Ribeirao Preto,Ribeirao Preto,SP 14040-904,Brazil.
FAU - Wegener, Gregers
AU  - Wegener G
AD  - 1Translational Neuropsychiatry Unit,Department of Clinical Medicine,Aarhus 
      University,8240 Risskov,Denmark.
FAU - Joca, Samia R L
AU  - Joca SRL
AD  - 1Translational Neuropsychiatry Unit,Department of Clinical Medicine,Aarhus 
      University,8240 Risskov,Denmark.
LA  - eng
PT  - Journal Article
DEP - 20190320
PL  - England
TA  - Acta Neuropsychiatr
JT  - Acta neuropsychiatrica
JID - 9612501
RN  - 0 (10,11-dihydroxy-N-n-propylnorapomorphine)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Indazoles)
RN  - 0 (Indole Alkaloids)
RN  - 0 (Isoquinolines)
RN  - 690G0D6V8H (Ketamine)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - AR2BHC0C6P (LY 235959)
RN  - E524N2IXA3 (Ornithine)
RN  - EC 1.14.13.39 (NOS1 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - N21FAR7B4S (Apomorphine)
RN  - UX0N37CMVH (7-nitroindazole)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/administration & dosage/*pharmacology
MH  - Apomorphine/administration & dosage/analogs & derivatives/pharmacology
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*pharmacology
MH  - Carbazoles/administration & dosage/pharmacology
MH  - Immobility Response, Tonic/drug effects
MH  - Indazoles/administration & dosage/pharmacology
MH  - Indole Alkaloids/administration & dosage/pharmacology
MH  - Isoquinolines/administration & dosage/pharmacology
MH  - Ketamine/administration & dosage/pharmacology
MH  - Locomotion/drug effects
MH  - Male
MH  - Microinjections
MH  - Nitric Oxide Synthase Type I/*antagonists & inhibitors
MH  - Ornithine/administration & dosage/pharmacology
MH  - Prefrontal Cortex/drug effects/metabolism
MH  - Rats
MH  - Receptor, trkB/antagonists & inhibitors/biosynthesis
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/administration & dosage/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/biosynthesis
OTO - NOTNLM
OT  - N-methyl-D-aspartate receptors
OT  - nitric oxide synthase
EDAT- 2019/03/21 06:00
MHDA- 2020/01/15 06:00
CRDT- 2019/03/21 06:00
PHST- 2019/03/21 06:00 [pubmed]
PHST- 2020/01/15 06:00 [medline]
PHST- 2019/03/21 06:00 [entrez]
AID - S092427081800039X [pii]
AID - 10.1017/neu.2018.39 [doi]
PST - ppublish
SO  - Acta Neuropsychiatr. 2019 Jun;31(3):143-150. doi: 10.1017/neu.2018.39. Epub 2019 
      Mar 20.