Ponciano R, Hallak J E C, Crippa J A, Guimarães F S, Bel Elaine Ap Del
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Department of Neurosciences and Behavioral Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Neurotox Res. 2024 Dec 19;43(1):2. doi: 10.1007/s12640-024-00724-0.
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.
长期使用典型抗精神病药物会根据分析时间的不同而导致不同的运动效应。急性治疗通常会诱发运动迟缓，类似于帕金森症，而反复使用则可能导致迟发性运动障碍，这是一种以不自主的口面部运动为特征的运动亢进综合征，例如小鼠的空嚼运动。迟发性运动障碍因其潜在的不可逆性和相关的运动不适而特别令人担忧。一种流行的理论认为，迟发性运动障碍是由氟哌啶醇等典型抗精神病药物的持续阻断导致D2型多巴胺能受体超敏引起的。此外，背外侧纹状体中炎症增加、氧化应激以及FosB蛋白表达升高也与其病理生理学有关。目前治疗迟发性运动障碍的方法往往疗效不明确，且可能导致严重的副作用。大麻二醇是一种具有抗氧化和抗炎特性的非致幻性大麻素，已对其潜在的抗运动障碍作用进行了研究。在本研究中，给小鼠注射3毫克/千克和10毫克/千克剂量的大麻二醇，以评估其预防、改善或逆转氟哌啶醇诱导的空嚼运动的能力。大麻二醇成功减少了空嚼运动，且不影响正常运动活动，不会加重氟哌啶醇诱导的运动迟缓，也不会自行诱发运动障碍效应。然而，在当前实验方案下，未观察到氟哌啶醇诱导的运动效应有明显逆转。此外，大麻二醇并未改变FosB表达或小胶质细胞形态。这些发现强调了进一步研究以探索大麻二醇治疗潜力的必要性，并有助于我们理解其在治疗迟发性运动障碍方面可能的临床应用。
