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

Deidiane Elisa Ribeiro, Plinio Cabrera Casarotto, Ailton Spiacci Júnior, Gabriel Gripp Fernandes, Lucas César Pinheiro, José Eduardo Tanus dos Santos, Hélio Zangrossi Júnior, Francisco Silveira Guimarães, Samia Regiane Lourenço Joca, Caroline Biojone

Research output: Contribution to journalArticleScientificpeer-review

Abstract

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 & Biological Psychiatry
ISSN0278-5846
DOIs
Publication statusPublished - 13 Apr 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • Nitric oxide
  • Panicolytic-like effect
  • BDNF
  • dPAG
  • 3112 Neurosciences

Cite this

Ribeiro, Deidiane Elisa ; Casarotto, Plinio Cabrera ; Júnior, Ailton Spiacci ; Fernandes, Gabriel Gripp ; Pinheiro, Lucas César ; dos Santos, José Eduardo Tanus ; Júnior, Hélio Zangrossi ; Guimarães, Francisco Silveira ; Joca, Samia Regiane Lourenço ; Biojone, Caroline. / Activation of the TRKB receptor mediates the panicolytic-like effect of the NOS inhibitor aminoguanidine. In: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2019.
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abstract = "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.",
keywords = "Nitric oxide, Panicolytic-like effect, BDNF, dPAG, 3112 Neurosciences",
author = "Ribeiro, {Deidiane Elisa} and Casarotto, {Plinio Cabrera} and J{\'u}nior, {Ailton Spiacci} and Fernandes, {Gabriel Gripp} and Pinheiro, {Lucas C{\'e}sar} and {dos Santos}, {Jos{\'e} Eduardo Tanus} and J{\'u}nior, {H{\'e}lio Zangrossi} and Guimar{\~a}es, {Francisco Silveira} and Joca, {Samia Regiane Louren{\cc}o} and Caroline Biojone",
year = "2019",
month = "4",
day = "13",
doi = "10.1016/j.pnpbp.2019.04.007",
language = "English",
journal = "Progress in Neuro-Psychopharmacology & Biological Psychiatry",
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Activation of the TRKB receptor mediates the panicolytic-like effect of the NOS inhibitor aminoguanidine. / Ribeiro, Deidiane Elisa; Casarotto, Plinio Cabrera; Júnior, Ailton Spiacci; Fernandes, Gabriel Gripp; Pinheiro, Lucas César; dos Santos, José Eduardo Tanus; Júnior, Hélio Zangrossi; Guimarães, Francisco Silveira; Joca, Samia Regiane Lourenço; Biojone, Caroline.

In: Progress in Neuro-Psychopharmacology & Biological Psychiatry, 13.04.2019.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Activation of the TRKB receptor mediates the panicolytic-like effect of the NOS inhibitor aminoguanidine

AU - Ribeiro, Deidiane Elisa

AU - Casarotto, Plinio Cabrera

AU - Júnior, Ailton Spiacci

AU - Fernandes, Gabriel Gripp

AU - Pinheiro, Lucas César

AU - dos Santos, José Eduardo Tanus

AU - Júnior, Hélio Zangrossi

AU - Guimarães, Francisco Silveira

AU - Joca, Samia Regiane Lourenço

AU - Biojone, Caroline

PY - 2019/4/13

Y1 - 2019/4/13

N2 - 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.

AB - 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.

KW - Nitric oxide

KW - Panicolytic-like effect

KW - BDNF

KW - dPAG

KW - 3112 Neurosciences

U2 - 10.1016/j.pnpbp.2019.04.007

DO - 10.1016/j.pnpbp.2019.04.007

M3 - Article

JO - Progress in Neuro-Psychopharmacology & Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology & Biological Psychiatry

SN - 0278-5846

ER -