HIV antiretroviral drug Efavirenz induces anxiety-like and depression-like behavior in rats: evaluation of neurotransmitter alterations in the striatum.

Autor: Cavalcante GI; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Chaves Filho AJ; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Linhares MI; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., de Carvalho Lima CN; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Venâncio ET; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Pharmacy Department, Faculty of Dentistry, Nursing and Pharmacy, Federal University of Ceará, Fortaleza, CE, Brazil., Rios ER; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Pharmacy Department, Faculty of Dentistry, Nursing and Pharmacy, Federal University of Ceará, Fortaleza, CE, Brazil., de Souza FC; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Vasconcelos SM; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Macêdo D; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., de França Fonteles MM; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Pharmacy Department, Faculty of Dentistry, Nursing and Pharmacy, Federal University of Ceará, Fortaleza, CE, Brazil. Electronic address: martafonteles@yahoo.com.br.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2017 Mar 15; Vol. 799, pp. 7-15. Date of Electronic Publication: 2017 Feb 08.
DOI: 10.1016/j.ejphar.2017.02.009
Abstrakt: Efavirenz (EFV) is an effective antiretroviral drug with a favorable pharmacokinetic profile and widely used in combination regimens to treat HIV infection. However, there are major concerns about the safety of this drug. Patients treated with EFV often experience neuropsychiatric adverse effects, which frequently lead to switching to alternative EFV-free regimens. The mechanisms involved in the central action of EFV are intrinsically unclear. Thus, this study aimed to investigate the effects of acute and subchronic (2 weeks) EFV administration in a series of behavioral tests for anxiety-like and depression-like behavior in healthy rats. We also evaluated the effect of EFV treatment in striatal concentrations of monoamine neurotransmitters (serotonin, dopamine and noradrenaline) and their metabolites and the amino acid neurotransmitters glutamate and GABA. Our results showed that acute treatment with EFV induced an anxiogenic-like effect, while sub-chronic treatment induced both anxiogenic-like and depressive-like behavior which was dose related.. Additionally, EFV treatment caused marked alterations in the striatal concentrations of monoamines and their metabolites (and turnover rates) and the amino acid neurotransmitters glutamate and GABA. These changes were influenced by treatment duration and dose. These findings add more evidence about the neuropsychiatric adverse effects of EFV and propose potential new mechanisms for the toxic action of this drug in the central nervous system.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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