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BDNF-TRKB signaling system of the dorsal periaqueductal gray matter is implicated in the panicolytic-like effect of antidepressant drugs.
Eur Neuropsychopharmacol. 2015 Jun; 25(6):913-22.EN

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.

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Authors+Show Affiliations

Casarotto PC
Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: plinio@gmx.com.
Santos PC
Department of Ophtamology, Otorhinolaringology and Head and Neck Surgery, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: paulafisiologia@gmail.com.
Lucas GA
Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: guilucas@fmrp.usp.br.
Biojone C
Department of Physics and Chemistry, Ribeirao Preto School of Pharmaceutical Sciences, University of Sao Paulo, Brazil. Electronic address: cbiojone@yahoo.com.br.
Pobbe RL
Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: rogerlhp10@gmail.com.
Vilela-Costa HH
Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: helohvilela@hotmail.com.
Joca SR
Department of Physics and Chemistry, Ribeirao Preto School of Pharmaceutical Sciences, University of Sao Paulo, Brazil. Electronic address: samia@usp.br.
Guimarães FS
Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: fsguimar@fmrp.usp.br.
Zangrossi H
Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil. Electronic address: zangross@fmrp.usp.br.

MeSH

Analysis of VarianceAnimalsAnti-Anxiety AgentsAntidepressive AgentsBrain-Derived Neurotrophic FactorCarbazolesDose-Response Relationship, DrugEnzyme InhibitorsEscape ReactionHippocampusIndole AlkaloidsInjections, Intra-ArticularMaleMaze LearningPeriaqueductal GrayRatsRats, WistarReaction TimeReceptor, trkBSignal TransductionTime Factors

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25840741

Citation

Casarotto, Plinio C., et al. "BDNF-TRKB Signaling System of the Dorsal Periaqueductal Gray Matter Is Implicated in the Panicolytic-like Effect of Antidepressant Drugs." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 25, no. 6, 2015, pp. 913-22.
Casarotto PC, Santos PC, Lucas GA, et al. BDNF-TRKB signaling system of the dorsal periaqueductal gray matter is implicated in the panicolytic-like effect of antidepressant drugs. Eur Neuropsychopharmacol. 2015;25(6):913-22.
Casarotto, P. C., Santos, P. C., Lucas, G. A., Biojone, C., Pobbe, R. L., Vilela-Costa, H. H., Joca, S. R., Guimarães, F. S., & Zangrossi, H. (2015). BDNF-TRKB signaling system of the dorsal periaqueductal gray matter is implicated in the panicolytic-like effect of antidepressant drugs. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 25(6), 913-22. https://doi.org/10.1016/j.euroneuro.2015.03.004
Casarotto PC, et al. BDNF-TRKB Signaling System of the Dorsal Periaqueductal Gray Matter Is Implicated in the Panicolytic-like Effect of Antidepressant Drugs. Eur Neuropsychopharmacol. 2015;25(6):913-22. PubMed PMID: 25840741.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BDNF-TRKB signaling system of the dorsal periaqueductal gray matter is implicated in the panicolytic-like effect of antidepressant drugs. AU - Casarotto,Plinio C, AU - Santos,Paula C dos, AU - Lucas,Guilherme A, AU - Biojone,Caroline, AU - Pobbe,Roger L H, AU - Vilela-Costa,Heloisa H, AU - Joca,Samia R L, AU - Guimarães,Francisco S, AU - Zangrossi,Hélio,Jr Y1 - 2015/03/17/ PY - 2014/04/28/received PY - 2015/02/24/revised PY - 2015/03/09/accepted PY - 2015/4/5/entrez PY - 2015/4/5/pubmed PY - 2016/2/18/medline KW - Antidepressants KW - BDNF KW - Dorsal periaqueductal gray KW - Fluoxetine KW - Imipramine KW - Panic SP - 913 EP - 22 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 25 IS - 6 N2 - 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. SN - 1873-7862 UR - https://www.unboundmedicine.com/medline/citation/25840741/BDNF_TRKB_signaling_system_of_the_dorsal_periaqueductal_gray_matter_is_implicated_in_the_panicolytic_like_effect_of_antidepressant_drugs_ DB - PRIME DP - Unbound Medicine ER -