Allopregnanolone induces antidepressant-like effects through BDNF-TrkB signaling independent from AMPA receptor activation in a rat learned helplessness model of depression.
Animals
Antidepressive Agents
/ pharmacology
Azepines
/ pharmacology
Behavior, Animal
/ drug effects
Benzamides
/ pharmacology
Brain-Derived Neurotrophic Factor
/ drug effects
Depression
/ drug therapy
Disease Models, Animal
Excitatory Amino Acid Antagonists
/ pharmacology
Helplessness, Learned
Male
Pregnanolone
/ pharmacology
Quinoxalines
/ pharmacology
Rats
Rats, Sprague-Dawley
Receptor, trkB
/ antagonists & inhibitors
Receptors, AMPA
/ antagonists & inhibitors
Signal Transduction
/ drug effects
AMPA receptor
Allopregnanolone (ALLO)
BDNF
Depression
Learned helplessness (LH)
TrkB
Journal
Behavioural brain research
ISSN: 1872-7549
Titre abrégé: Behav Brain Res
Pays: Netherlands
ID NLM: 8004872
Informations de publication
Date de publication:
15 07 2020
15 07 2020
Historique:
received:
28
02
2020
revised:
12
04
2020
accepted:
20
04
2020
pubmed:
22
5
2020
medline:
26
10
2021
entrez:
22
5
2020
Statut:
ppublish
Résumé
Allopregnanolone (ALLO, 3α5α-tetrahydroprogesterone) was found to be effective for depressed patients. Animal models of depression indicate that ALLO is associated with the pathophysiology of depression. Traditional antidepressant drugs produce antidepressant effects via the monoamine system, with consequent up-regulation of brain-derived neurotrophic factor (BDNF). This study was designed to examine whether the antidepressant effects of ALLO involve BDNF-TrkB signaling or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activation on the learned helplessness paradigm. The antidepressant-like effect of ALLO infusion into the cerebral ventricle was blocked by coinfusion of TrkB inhibitor ANA-12, but not by co-administration of AMPA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfoamoylbenzo(f)quinoxaline (NBQX). Thus, the antidepressant-like effect of ALLO involves BDNF signaling independent from AMPA receptor activation.
Identifiants
pubmed: 32437888
pii: S0166-4328(20)30369-7
doi: 10.1016/j.bbr.2020.112670
pii:
doi:
Substances chimiques
ANA 12 compound
0
Antidepressive Agents
0
Azepines
0
Benzamides
0
Brain-Derived Neurotrophic Factor
0
Excitatory Amino Acid Antagonists
0
Quinoxalines
0
Receptors, AMPA
0
2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
118876-58-7
Pregnanolone
BXO86P3XXW
Receptor, trkB
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112670Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None.