Activation of the TRKB receptor mediates the panicolytic-like effect of the NOS inhibitor aminoguanidine

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  • Deidiane Elisa Ribeiro
  • Plinio Cabrera Casarotto, Universidade de São Paulo – USP, Helsingin yliopisto
  • ,
  • Ailton Jr Spiacci, Universidade de São Paulo – USP
  • ,
  • Gabriel Gripp Fernandes, Universidade de São Paulo – USP
  • ,
  • Lucas César Pinheiro, Universidade de São Paulo – USP
  • ,
  • José Eduardo Tanus-Santos, Universidade de São Paulo – USP
  • ,
  • Hélio Jr Zangrossi, Universidade de São Paulo – USP
  • ,
  • Francisco Silveira Guimarães, Universidade de São Paulo – USP
  • ,
  • Samia Regiane Lourenço Joca
  • Caroline Biojone, Helsingin yliopisto, Universidade de São Paulo – USP

Nitric oxide (NO) triggers escape reactions in the dorsal periaqueductal gray matter (dPAG), a core structure mediating panic-associated response, and decreases the release of BDNF in vitro. BDNF mediates the panicolytic effect induced by antidepressant drugs and produces these effects per se when injected into the dPAG. Based on these findings, we hypothesize that nitric oxide synthase (NOS) inhibitors would have panicolytic properties associated with increased BDNF signaling in the dPAG. We observed that the repeated (7 days), but not acute (1 day), systemic administration of the NOS inhibitor aminoguanidine (AMG; 15 mg/kg/day) increased the latency to escape from the open arm of the elevated T-maze (ETM) and inhibited the number of jumps in hypoxia-induced escape reaction in rats, suggesting a panicolytic-like effect. Repeated, but not acute, AMG administration (15 mg/kg) also decreased nitrite levels and increased TRKB phosphorylation at residues Y706/7 in the dPAG. Notwithstanding the lack of AMG effect on total BDNF levels in this structure, the microinjection of the TRK antagonist K252a into the dPAG blocked the anti-escape effect of this drug in the ETM. Taken together our data suggest that the inhibition of NO production by AMG increases the levels of pTRKB, which is required for the panicolytic-like effect observed.

Original languageEnglish
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume93
IssueJuly
Pages (from-to)232-239
Number of pages8
ISSN0278-5846
DOIs
Publication statusPublished - 2019

    Research areas

  • BDNF, dPAG, Nitric oxide, Panicolytic-like effect

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