Effects of tropicamide on catalepsy and motor function in a mouse model of Parkinson’s disease

Corrêa, Érica M. S.; Souza, Albert S.; Christofoletti, Gustavo*

Faculty of Medicine, Institute of Health, Federal University of Mato Grosso do Sul, Campo Grande, Brazil

Abstract

Parkinson’s disease is a progressive disorder characterized by dopaminergic neuronal apoptosis in the basal ganglia. The prevalence of this condition increases with age. A key deficit in Parkinson’s disease is the loss of automaticity, which affects the patients’ daily activities. Levodopa is the most effective treatment for Parkinson’s disease. However, because it is not effective for all patients in later stages of the disease, new approaches have been proposed. This study investigated the effects of tropicamide, an M4 muscarinic receptor antagonist, on catalepsy and gait in an animal model of Parkinson’s disease. Two experiments were conducted. In both experiments, animals were injected with either haloperidol to induce Parkinson’s disease-like symptoms or saline as a placebo for the control group. In Experiment I, animals received an intraperitoneal injection of either tropicamide (the experimental intervention) or saline (the placebo). In Experiment II, tropicamide or saline was administered intracerebrally instead of intraperitoneally. Catalepsy was assessed using the Bar Test and gait was evaluated using the open field test. Haloperidol induced catalepsy and motor impairments resembling those observed in Parkinson’s disease. Tropicamide administration, both intraperitoneally and intracerebrally, reversed haloperidol-induced deficits. These findings suggest that tropicamide can potentially mitigate Parkinson’s disease-related motor impairment. They also suggest a strong interaction between the M4 muscarinic receptors and dopaminergic pathways in the basal ganglia. These results underscore the importance of developing new pharmacological strategies targeting M4 muscarinic receptors in patients with Parkinson’s disease.

托吡卡胺改善帕金森病小鼠模型运动功能

摘要

帕金森病的一个主要缺陷是丧失自动性，这影响了患者的日常活动。左旋多巴是治疗帕金森病最有效的药物。然而，由于左旋多巴并非对所有晚期患者都有效，因此有人提出了新的治疗方法。实验旨在了解托吡卡胺（一种M4毒蕈碱受体拮抗剂）对帕金森病动物模型中强直性昏厥和步态的影响。实验分为2个部分，动物均注射氟哌啶醇以诱发类似帕金森病的症状，或注射生理盐水作为安慰剂作为对照组。在实验 I 中，动物腹腔注射托吡卡胺（实验干预）或生理盐水（安慰剂）。在实验 II 中，托吡卡胺或生理盐水经脑内注射，而不是经腹腔注射。结果发现，氟哌啶醇可诱发类似于帕金森病的强直性昏厥和运动障碍。腹腔注射和脑内注射托吡卡胺可逆转氟哌啶醇引起的障碍。这些结果表明，托吡卡胺可减轻与帕金森病相关的运动功能障碍，从而强调针对帕金森病患者的M4毒蕈碱受体有潜力开发新药理策略。