Cannabigerol Mitigates Haloperidol-Induced Vacuous Chewing Movements in Mice

Author(s)

Ponciano, R. ; Hallak, J. E. C. ; Crippa, J. A. ; Guimaraes, F. S. ; Del Bel, Elaine Ap.

• Document type: Journal article
• Source: NEUROTOXICITY RESEARCH; v. 43, n. 1, p. 12-pg., 2025-02-01.

Abstract

Chronic use of typical antipsychotics can lead to varying motor effects depending on the timing of analysis. Acute treatment typically induces hypokinesia, resembling parkinsonism, while repeated use can result in tardive dyskinesia, a hyperkinetic syndrome marked by involuntary orofacial movements, such as vacuous chewing movements in mice. Tardive dyskinesia is particularly concerning due to its potential irreversibility and associated motor discomfort. One prevailing theory suggests that tardive dyskinesia arises from hypersensitivity of D2-type dopaminergic receptors caused by continuous blockade from typical antipsychotics like haloperidol. Additionally, increased inflammation, oxidative stress, and elevated FosB protein expression in the dorsolateral striatum are implicated in its pathophysiology. Current treatments for tardive dyskinesia often lack clear efficacy and may lead to significant side effects. Cannabigerol, a non-psychotomimetic cannabinoid with antioxidant and anti-inflammatory properties, has been investigated for its potential antidyskinetic effects. In this study, mice were treated with cannabigerol at doses of 3 and 10 mg/kg to evaluate its ability to prevent, ameliorate, or reverse haloperidol-induced vacuous chewing movements. Cannabigerol successfully reduced vacuous chewing movements without affecting normal motor activity, exacerbating haloperidol-induced hypokinesia, or inducing dyskinetic effects on its own. However, no significant reversal of the haloperidol-induced motor effects was observed under the current protocol. Furthermore, cannabigerol did not alter FosB expression or microglia morphology. These findings underscore the need for further research to explore cannabigerol's therapeutic potential and contribute to our understanding of its possible clinical applications in managing tardive dyskinesia. (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
• FAPESP's process: 23/16182-2 - Cannabidiol in the treatment of neuropsychiatric disorders: new paths
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants