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

Publication date: Available online 13 April 2019Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): 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 BiojoneAbstractNitric 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 anta...

Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - April 15, 2019 Category: Psychiatry Source Type: research