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GABA A /benzodiazepine receptors in the dorsal periaqueductal gray mediate the panicolytic but not the anxiolytic effect of alprazolam in rats.
- 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.)
- Subjects :
- Animals
Anti-Anxiety Agents pharmacology
Antidepressive Agents pharmacology
Anxiety drug therapy
Anxiety metabolism
Benzodiazepines pharmacology
Bicuculline pharmacology
Escape Reaction drug effects
Flumazenil pharmacology
GABA-A Receptor Antagonists pharmacology
Male
Panic physiology
Panic Disorder drug therapy
Periaqueductal Gray metabolism
Rats
Rats, Wistar
Receptors, GABA-A metabolism
gamma-Aminobutyric Acid pharmacology
Alprazolam pharmacology
Panic drug effects
Periaqueductal Gray drug effects
Subjects
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