Pharmacological evaluation of NO/cGMP/KATP channels pathway in the antidepressant-like effect of carbamazepine in mice.
Animals
Anticonvulsants
/ administration & dosage
Antidepressive Agents
/ administration & dosage
Carbamazepine
/ administration & dosage
Cyclic GMP
/ metabolism
Depression
/ drug therapy
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Synergism
Fluoxetine
/ administration & dosage
KATP Channels
/ metabolism
Locomotion
/ drug effects
Male
Mice
Nitric Oxide
/ metabolism
Swimming
Journal
Behavioural pharmacology
ISSN: 1473-5849
Titre abrégé: Behav Pharmacol
Pays: England
ID NLM: 9013016
Informations de publication
Date de publication:
01 02 2021
01 02 2021
Historique:
pubmed:
9
12
2020
medline:
15
12
2021
entrez:
8
12
2020
Statut:
ppublish
Résumé
Carbamazepine, an anticonvulsant drug, has shown antidepressant effects in clinical and experimental models. Nitric oxide (NO) is a neurotransmitter in the central nervous system and has been involved in a variety of diseases including depression. In the present study, the involvement of NO/cyclic GMP/KATP channels pathway in the antidepressant action of carbamazepine was investigated in mice. The antidepressant-like activity was assessed in the forced swim test (FST) behavioral paradigm. Carbamazepine reduced (40 mg/kg, intraperitoneal) immobility period. The antidepressant-like effect of carbamazepine (40 mg/kg, intraperitoneal) was prevented by pretreatment with L-arginine [substrate for NO synthase (NOS), 750 mg/kg, intraperitoneal], sildenafil (a PDE-5 inhibitor, 5 mg/kg, intraperitoneal) and diazoxide (K+ channels opener, 10 mg/kg). Pretreatment of mice with L-NAME (a non-selective NOS inhibitor, 10 mg/kg, intraperitoneal), methylene blue (direct inhibitor of both NOS and soluble guanylate cyclase, 10 mg/kg, intraperitoneal) and glibenclamide (an ATP-sensitive K+ channel blocker, 1 mg/kg, intraperitoneal) produced potentiation of the action of a sub-effective dose of carbamazepine (30 mg/kg, intraperitoneal). Also, carbamazepine (30 mg/kg) potentiated the antidepressant-like effect of fluoxetine through NO modulation. The various modulators used in the study did not produce any changes in locomotor activity per se. The results demonstrated that the antidepressant-like effect of carbamazepine in the FST involved an interaction with the NO/cGMP/KATP channels pathway.
Identifiants
pubmed: 33290345
pii: 00008877-202102000-00005
doi: 10.1097/FBP.0000000000000600
doi:
Substances chimiques
Anticonvulsants
0
Antidepressive Agents
0
KATP Channels
0
Fluoxetine
01K63SUP8D
Nitric Oxide
31C4KY9ESH
Carbamazepine
33CM23913M
Cyclic GMP
H2D2X058MU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
32-42Informations de copyright
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
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