Involvement of dopamine D 2 and glutamate NMDA receptors in the antidepressant-like effect of amantadine in mice.

Autor: Raupp-Barcaro IFM; Department of Pharmacology, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico, C.P. 19031, Curitiba, Paraná, 81540-990, Brazil., da Silva Dias IC; Department of Pharmacology, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico, C.P. 19031, Curitiba, Paraná, 81540-990, Brazil., Meyer E; Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, Maringá, Paraná, 87020-900, Brazil., Vieira JCF; Department of Pharmacology, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico, C.P. 19031, Curitiba, Paraná, 81540-990, Brazil., da Silva Pereira G; Department of Pharmacology, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico, C.P. 19031, Curitiba, Paraná, 81540-990, Brazil., Petkowicz AR; Department of Pharmacology, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico, C.P. 19031, Curitiba, Paraná, 81540-990, Brazil., de Oliveira RMW; Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, Maringá, Paraná, 87020-900, Brazil., Andreatini R; Department of Pharmacology, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico, C.P. 19031, Curitiba, Paraná, 81540-990, Brazil. Electronic address: randreatini@ufpr.br.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2021 Sep 10; Vol. 413, pp. 113443. Date of Electronic Publication: 2021 Jul 01.
DOI: 10.1016/j.bbr.2021.113443
Abstrakt: The present study investigated the pharmacological mechanisms of the antidepressant-like effects of amantadine in mice and their influence on hippocampal neurogenesis. To improve the translational validity of preclinical results, reproducibility across laboratories and replication in other animal models and species are crucial. Single amantadine administration at doses of 50 and 75 mg/kg resulted in antidepressant-like effects in mice in the tail suspension test (TST), reflected by an increase in immobility time. The effects of amantadine were seen at doses that did not alter locomotor activity. The tyrosine hydroxylase inhibitor α-methyl-ρ-tyrosine did not influence the anti-immobility effect of amantadine in the TST. Pretreatment with the α 1 adrenergic receptor antagonist prazosin, β adrenergic receptor antagonist propranolol, α 2 adrenergic receptor antagonist yohimbine, and α 2 adrenergic receptor agonist clonidine did not alter the antidepressant-like effect of amantadine. However, amantadine's effect was blocked by the dopamine D 2 receptor antagonist haloperidol and glutamate receptor agonist N-methyl-D-aspartate (NMDA). Repeated amantadine administration (50 mg/kg) also exerted an antidepressant-like effect, paralleled by an increase in hippocampal neurogenesis. The present results demonstrate that the antidepressant-like effects of amantadine may be mediated by its actions on D 2 and NMDA receptors and likely involve hippocampal neurogenesis.
(Copyright © 2021. Published by Elsevier B.V.)
Databáze: MEDLINE
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