Cannabigerol Mitigates Haloperidol-Induced Vacuous Chewing Movements in Mice

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 due to continuous blockade by typical antipsychotics like haloperidol. Additionally, factors such 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 effectiveness and can 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 did not induce dyskinetic effects on its own and successfully reduced vacuous chewing movements without impacting normal motor activity or exacerbating haloperidol-induced hypokinesia. However, no significant reversal of the symptoms 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 fully explore cannabigerol's therapeutic potential, contributing to our understanding of its possible clinical applications in managing tardive dyskinesia.