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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Protective role of endocannabinoid signaling in an animal model of haloperidol-induced tardive dyskinesia

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Autor(es):
Ropke, Jivago [1] ; Ferreira-Vieira, Talita H. [2] ; Iglesias, Lia P. [1] ; Asth, Laila [1] ; Ribeiro, Fabiola M. [2] ; Moreira, Fabricio A. [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Fed Minas Gerais UFMG, Inst Biol Sci, Dept Pharmacol, Ave Pres Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG - Brazil
[2] Univ Fed Minas Gerais UFMG, Inst Biol Sci, Dept Biochem & Immunol, Belo Horizonte, MG - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Pharmacology Biochemistry and Behavior; v. 206, JUL 2021.
Citações Web of Science: 0
Resumo

Tardive dyskinesia (TD) is a side effect associated with the long-term use of certain antipsychotics. Considering the modulatory role of the endocannabinoid system upon dopaminergic neurotransmission, the present study tested the hypothesis that increasing endocannabinoid (anandamide and 2-arachidonoylglycerol) levels attenuates haloperidol-induced TD (vacuous chewing movements, VCMs) in male Wistar rats. The animals received administration of chronic haloperidol (38 mg/kg; 29 days) followed by acute FAAH (URB597, 0.1 \& ndash;0.5 mg/kg) or MAGL (JZL184, 1 \& ndash;10 mg/kg) inhibitors before VCM quantification. The underlying mechanisms were evaluated by pre-treatments with a CB1 receptor antagonist (AM251, 1 mg/kg) or a TRPV1 channel blocker (SB366791, 1 mg/kg). Moreover, CB1 receptor expression was evaluated in the striatum of high-VCM animals. As expected, haloperidol induced VCMs only in a subset of rats. Either FAAH or MAGL inhibition reduced VCMs. These effects were prevented by CB1 receptor antagonism, but not by TRPV1 blockage. Remarkably, CB1 receptor expression was increased high-VCM rats, with a positive correlation between the levels of CB1 expression and the number of VCMs. In conclusion, increasing endocannabinoid levels results in CB1 receptor-mediated protection against haloperidol-induced TD in rats. The increased CB1 receptor expression after chronic haloperidol treatment suggests a counter-regulatory protective mechanism. (AU)

Processo FAPESP: 17/24304-0 - Novas perspectivas no emprego de fármacos que modificam neurotransmissores atípicos no tratamento de transtornos neuropsiquiátricos
Beneficiário:Francisco Silveira Guimaraes
Linha de fomento: Auxílio à Pesquisa - Temático