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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Ropke, Jivago [1] ; Ferreira-Vieira, Talita H. [2] ; Iglesias, Lia P. [1] ; Asth, Laila [1] ; Ribeiro, Fabiola M. [2] ; Moreira, Fabricio A. [1]
Total Authors: 6
[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
Total Affiliations: 2
Document type: Journal article
Source: Pharmacology Biochemistry and Behavior; v. 206, JUL 2021.
Web of Science Citations: 0

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)

FAPESP's process: 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders
Grantee:Francisco Silveira Guimaraes
Support type: Research Projects - Thematic Grants