title: BDNF-TRKB signaling system of the dorsal periaqueductal gray matter is implicated in the panicolytic-like effect of antidepressant drugs.
abstract: A wealth of evidence implicates the BDNF-TRKB system in the therapeutic effects of antidepressant drugs (ADs) on mood disorders. However, little is known about the involvement of this system in the panicolytic property also exerted by these compounds. In the present study we evaluated the participation of the BDNF-TRKB system of the dorsal periaqueductal gray matter (DPAG), a core structure involved in the pathophysiology of panic disorder, in AD-induced panicolytic-like effects in rats. The results showed that short- (3 days) or long-term (21 days) systemic treatment with the tricyclic ADs imipramine, clomipramine or desipramine increased BDNF levels in the DPAG. Only longterm treatment with the selective serotonin reuptake inhibitor fluoxetine was able to increase BDNF levels in this structure. After 21-day treatment, fluoxetine and the three tricyclic ADs used also increased BDNF concentration in the hippocampus, a key area implicated in their mood-related actions. Neither in the DPAG nor hippocampus did long-term treatment with the standard anxiolytics diazepam, clonazepam or buspirone affect BDNF levels. Imipramine, both after short and long-term administration, and fluoxetine under the latter regimen, raised the levels of phosphorylated TRKB in the DPAG. Short-term treatment with imipramine or BDNF microinjection inhibited escape expression in rats exposed to the elevated T maze, considered as a panicolytic-like effect. This anti-escape effect was attenuated by the intra-DPAG administration of the TRK receptor antagonist k252a. Altogether, our data suggests that facilitation of the BDNF-TRKB system in the DPAG is implicated in the panicolytic effect of ADs.
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: plinio@gmx.com.
authors.forename: Plinio C
authors.initials: PC
authors.lastname: Casarotto
authors.affiliation: Department of Ophtamology, Otorhinolaringology and Head and Neck Surgery, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: paulafisiologia@gmail.com.
authors.forename: Paula C dos
authors.initials: PC
authors.lastname: Santos
authors.affiliation: Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: guilucas@fmrp.usp.br.
authors.forename: Guilherme A
authors.initials: GA
authors.lastname: Lucas
authors.affiliation: Department of Physics and Chemistry, Ribeirao Preto School of Pharmaceutical Sciences, University of Sao Paulo, Brazil. Electronic address: cbiojone@yahoo.com.br.
authors.forename: Caroline
authors.initials: C
authors.lastname: Biojone
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: rogerlhp10@gmail.com.
authors.forename: Roger L H
authors.initials: RL
authors.lastname: Pobbe
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: helohvilela@hotmail.com.
authors.forename: Heloisa H
authors.initials: HH
authors.lastname: Vilela-Costa
authors.affiliation: Department of Physics and Chemistry, Ribeirao Preto School of Pharmaceutical Sciences, University of Sao Paulo, Brazil. Electronic address: samia@usp.br.
authors.forename: Samia R L
authors.initials: SR
authors.lastname: Joca
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: fsguimar@fmrp.usp.br.
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Guimarães
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: zangross@fmrp.usp.br.
authors.forename: Hélio
authors.initials: H
authors.lastname: Zangrossi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004924:Escape Reaction / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D026121:Indole Alkaloids / Q000494:pharmacology; D007270:Injections, Intra-Articular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D020813:Receptor, trkB / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; C049985:staurosporine aglycone; D020813:Receptor, trkB
keywords: Antidepressants; BDNF; Dorsal periaqueductal gray; Fluoxetine; Imipramine; Panic