Psychosis in Parkinson's disease is a common phenomenon associated with poor outcomes. To clarify the pathophysiology of this condition and the mechanisms of antipsychotic treatments, we have here characterized the neurophysiological brain states induced by clozapine, pimavanserin, and the novel prospective antipsychotic mesdopetam in a rodent model of Parkinson's disease psychosis, based on chronic dopaminergic denervation by 6-OHDA lesions, levodopa priming, and the acute administration of an NMDA antagonist. Parallel recordings of local field potentials from eleven cortical and sub-cortical regions revealed shared neurophysiological treatment effects for the three compounds, despite their different pharmacological profiles, involving reversal of features associated with the psychotomimetic state, such as a reduction of aberrant high-frequency oscillations in prefrontal structures together with a decrease of abnormal synchronization between different brain regions. Other drug-induced neurophysiological features were more specific to each treatment, affecting network oscillation frequencies and entropy, pointing to discrete differences in mechanisms of action. These findings indicate that neurophysiological characterization of brain states is particularly informative when evaluating therapeutic mechanisms in conditions involving symptoms that are difficult to assess in rodents such as psychosis, and that mesdopetam should be further explored as a potential novel antipsychotic treatment option for Parkinson psychosis.

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美多培坦、匹马范色林和氯氮平对帕金森病精神病啮齿动物模型的神经生理治疗作用

帕金森病中的精神病是一种与不良预后相关的常见现象。为了阐明这种情况的病理生理学和抗精神病药物治疗的机制，我们在此基于慢性多巴胺能去神经支配，在帕金森病精神病啮齿动物模型中描述了氯氮平、匹马范色林和新型前瞻性抗精神病药物美多培坦诱导的神经生理学大脑状态。 -OHDA 损伤、左旋多巴启动和 NMDA 拮抗剂的急性给药。来自十一个皮质和皮质下区域的局部场电位的并行记录揭示了这三种化合物的共同神经生理学治疗效果，尽管它们的药理特征不同，包括逆转与拟心理状态相关的特征，例如减少异常高频振荡前额叶结构的变化以及不同大脑区域之间异常同步的减少。其他药物引起的神经生理学特征对于每种治疗都更加具体，影响网络振荡频率和熵，表明作用机制存在离散差异。这些发现表明，在评估涉及啮齿类动物难以评估的症状（例如精神病）的治疗机制时，大脑状态的神经生理学特征特别有用，并且应进一步探索美多培坦作为帕金森精神病的潜在新型抗精神病治疗选择。