Inhibition of neuronal Nitric Oxide Synthase in the rat prelimbic cortex induces antidepressant-like effects independently of BDNF-TrkB-mTOR signaling

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  • Vitor Silva Pereira
  • ,
  • Angélica Romano, School of Pharmaceutical Sciences of Ribeirão Preto, 14040-903, Ribeirão Preto, São Paulo, Brazil., Brazil
  • Gregers Wegener
  • Sâmia Joca
NMDA antagonists and nitric oxide synthase (NOS) inhibitors induce antidepressant-like effects and may represent alternative treatment options for depression. The behavioral effects of NMDA antagonists, such as ketamine, 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 behavioral effects of NOS inhibitors. Therefore, this work aimed at determining the role of TrkB and mTOR signaling in the prelimbic area of the ventral mPFC (vmPFC-PL) in the antidepressant-like effect of NOS inhibitors. We found that bilateral injection of BDNF into the vmPFC-PL induced an antidepressant-like effect, which was blocked by pretreatment with K252a (Trk antagonist) and rapamycin (mTOR inhibitor). Microinjection of NMDA antagonist (LY 235959) into the vmPFC-PL induced antidepressant-like effect that was suppressed by local rapamycin but not by K252a pretreatment. Microinjection of a NOS inhibitor (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. Our data support the hypothesis that NMDA blockade induces an antidepressant-like effect that requires mTOR but not Trk signaling into the vmPFC-PL. Moreover, the antidepressant-like effect induced by local NOS inhibition seems to be independent on both Trk and mTOR signaling in the vmPFC-PL.
Original languageEnglish
JournalActa Neuropsychiatrica
Publication statusAccepted/In press - 2019

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