Back to Search Start Over

GABA A /benzodiazepine receptors in the dorsal periaqueductal gray mediate the panicolytic but not the anxiolytic effect of alprazolam in rats.

Authors :
Frias AT
Fernandes GG
Zangrossi H Jr
Source :
Behavioural brain research [Behav Brain Res] 2019 May 17; Vol. 364, pp. 99-105. Date of Electronic Publication: 2019 Feb 12.
Publication Year :
2019

Abstract

Although the etiology of panic disorder (PD) remains elusive, accumulating evidence suggests a key role for the dorsal periaqueductal gray matter (dPAG). There is also evidence that this midbrain area is critically involved in mediation of the panicolytic effect of antidepressants, which with high potency benzodiazepines (e.g. alprazolam and clonazepam) are first line treatment for PD. Whether the dPAG is also implicated in the antipanic effect of the latter drugs is, however, still unknown. We here investigated the consequences of blocking GABA <subscript>A</subscript> or benzodiazepine receptors within the dPAG, with bicuculline (5 pmol) and flumazenil (80 nmol), respectively, on the panicolytic and anxiolytic effects of alprazolam (4 mg/kg). Microinjection of these antagonists fully blocked the anti-escape effect, considered as a panicolytic-like action, caused by a single systemic injection of alprazolam in male Wistar rats submitted to the elevated T-maze. These antagonists, however, did not affect the anxiolytic effect of the benzodiazepine on inhibitory avoidance acquisition and punished responding, measured in the elevated T-maze and Vogel conflict tests, respectively. Altogether, our findings show the involvement of GABA <subscript>A</subscript> /benzodiazepine receptors of the dPAG in the panicolytic, but not the anxiolytic effect caused by alprazolam. They also implicate the dPAG as the fulcrum of the effects of different classes of clinically effective antipanic drugs.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1872-7549
Volume :
364
Database :
MEDLINE
Journal :
Behavioural brain research
Publication Type :
Academic Journal
Accession number :
30768992
Full Text :
https://doi.org/10.1016/j.bbr.2019.02.016