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Effect of cannabigerol in haloperidol-induced tardive dyskinesia model

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Rafaela Aparecida Ponciano da Silva de Moraes
Total Authors: 1
Document type: Master's Dissertation
Press: Ribeirão Preto.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
Defense date:
Examining board members:
Elaine Aparecida Del Bel Belluz Guimaraes; Marcela Bermudez Echeverry; Felipe Villela Gomes
Advisor: Elaine Aparecida Del Bel Belluz Guimaraes

The introduction of antipsychotics in the 1950s allowed the treatment of symptoms of schizophrenia, such as delusions and hallucinations. However, the chronicity of treatment with the typical antipsychotics induces motor effects such as tardive dyskinesia, characterized by involuntary and stereotyped orofacial movements of great functional and social impact. Tardive dyskinesia is a target of several studies due to its potential irreversibility and its uncomfortable nature for the patient. One of the hypotheses to explain the pathophysiology of this effect is based on the hypersensitivity of D2-type dopaminergic receptors to their constant blockade by typical antipsychotics, such as haloperidol. There would also be an increase in inflammatory processes and oxidative stress. Furthermore, it is known that repeated treatment with haloperidol increases the expression of the FosB protein in the dorsolateral striatum of rodents, which would be related to the induction of involuntary oral movements.Studies by our group point out that cannabinoids have an atypical antipsychotic profile, that is, they have a therapeutic effect on the classic symptoms of schizophrenia without leading to increased FosB expression in the dorsolateral striatum and the appearance of motor symptoms. Furthermore, cannabidiol attenuated the haloperidol-induced involuntary oral movements. Cannabigerol, another phytocannabinoid, has not yet been tested in the tardive dyskinesia model. However, it shares with cannabidiol a profile of interactions that gives it an antioxidant and anti-inflammatory effect, which suggests that this compound also has an antidyskinetic potential. Based on these premises, this study aimed to (i) delineate temporal and dose-response curves for haloperidol and, based on this, establish a model of tardive dyskinesia; (ii) investigate the antidyskinetic effect of cannabigerol in this preclinical model and, once this effect is confirmed, (iii) investigate whether it would be associated with its anti-inflammatory action and (iv) characterize the expression of FosB in the striatum of animals after the treatment with cannabigerol and relate this expression profile with its effect on the model. The results showed that cannabigerol has no dyskinetic effect per se and at doses of 3 and 10mg/kg it attenuated involuntary oral movements in mice without altering their motor activity. No reversal effect of cannabigerol was observed in the model. The attenuation effect is not related to the decrease in haloperidol-induced FosB expression in the dorsolateral striatum, and no alterations in microglia morphology and density were observed either. Further studies are needed to better investigate this effect, however this work presents contributions for a better understanding of cannabigerol, with possible clinical applications. (AU)

FAPESP's process: 21/02873-8 - Cannabinoids and doxycycline interaction in an experimental tardive dyskinesia model
Grantee:Rafaela Aparecida Ponciano da Silva de Moraes
Support Opportunities: Scholarships in Brazil - Master