Isradipine, an L-type calcium channel blocker, attenuates cocaine effects in mice by reducing central glutamate release.

Autor: Lima ALD; Department of Pharmacology, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Silva EG; Department of Immunology and Biochemistry, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Cardozo PL; Department of Immunology and Biochemistry, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., da Silva MCM; Department of Pharmacology, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Koerich S; Department of Pharmacology, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Ribeiro FM; Department of Immunology and Biochemistry, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Moreira FA; Department of Pharmacology, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Vieira LB; Department of Pharmacology, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address: lubvieira@icb.ufmg.br.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 May 15; Vol. 971, pp. 176489. Date of Electronic Publication: 2024 Mar 15.
DOI: 10.1016/j.ejphar.2024.176489
Abstrakt: Substance abuse disorder is a chronic condition for which pharmacological treatment options remain limited. L-type calcium channels (LTCC) have been implicated in drug-related plasticity and behavior. Specifically, dopaminergic neurons in the mesocorticolimbic pathway express Ca v 1.2 and Ca v 1.3 channels, which may regulate dopaminergic activity associated with reward behavior. Therefore, this study aimed to investigate the hypothesis that pre-administration of the LTCC blocker, isradipine can mitigate the effects of cocaine by modulating central glutamatergic transmission. For that, we administered isradipine at varying concentrations (1, 7.5, and 15 μg/μL) via intracerebroventricular injection in male Swiss mice. This pretreatment was carried out prior to subjecting animals to behavioral assessments to evaluate cocaine-induced locomotor sensitization and conditioned place preference (CPP). The results revealed that isradipine administered at a concentration of 1 μg/μL effectively attenuated both the sensitization and CPP induced by cocaine (15 mg/kg, via i. p.). Moreover, mice treated with 1 μg/μL of isradipine showed decreased presynaptic levels of glutamate and calcium in the cortex and hippocampus as compared to control mice following cocaine exposure. Notably, the gene expression of ionotropic glutamate receptors, AMPA, and NMDA, remained unchanged, as did the expression of Ca v 1.2 and Ca v 1.3 channels. Importantly, these findings suggest that LTCC blockage may inhibit behavioral responses to cocaine, most likely by decreasing glutamatergic input in areas related to addiction.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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