HIV antiretroviral drug Efavirenz induces anxiety-like and depression-like behavior in rats: evaluation of neurotransmitter alterations in the striatum
| Autor: | Adriano José Maia Chaves Filho, Silvânia Maria Mendes Vasconcelos, Danielle Silveira Macêdo, Camila Nayane de Carvalho Lima, Emiliano Ricardo Vasconcelos Rios, Giuliana Ignácio Teixeira Cavalcante, Marta Maria de França Fonteles, Maria Isabel Linhares, Francisca Cléa Florenço de Souza, E.T. Venâncio |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Drug Cyclopropanes Male Efavirenz Time Factors Anti-HIV Agents media_common.quotation_subject Pharmacology Anxiety 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Dopamine Medicine Animals Rats Wistar Adverse effect Neurotransmitter Maze Learning media_common Neurotransmitter Agents business.industry Depression Glutamate receptor Benzoxazines Rats Neostriatum 030104 developmental biology Monoamine neurotransmitter chemistry Alkynes Serotonin business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | European journal of pharmacology. 799 |
| ISSN: | 1879-0712 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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