Tremor is one of the motor symptoms of Parkinson’s disease (PD), present also in neuroleptic-induced parkinsonism. Tremulous Jaw Movements (TJMs) are suggested to be a well-validated rodent model of PD resting tremor. TJMs can be induced by typical antipsychotics and are known to be reduced by different drugs, including adenosine A_2A receptor antagonists. The aim of the present study was to search for brain structures involved in the tremorolytic action of SCH58261, a selective A_2A receptor antagonist, in TJMs induced by subchronic pimozide. Besides TJMs, we evaluated in the same animals the expression of zif-268 mRNA (neuronal responsiveness marker), and mRNA levels for glutamic acid decarboxylase 65-kDa isoform (GAD65) and vesicular glutamate transporters 1 and 2 (vGluT1/2) in selected brain structures, as markers of GABAergic and glutamatergic neurons, respectively. We found that SCH58261 reduced the pimozide-induced TJMs. Pimozide increased the zif-268 mRNA level in the striatum, nucleus accumbens (NAc) core, and substantia nigra pars reticulata (SNr). Additionally, it increased GAD65 mRNA in the striatum and SNr, and vGluT2 mRNA levels in the subthalamic nucleus (STN). A positive correlation between zif-268, GAD65 and vGluT2 mRNAs and TJMs was found. SCH58261 reversed the pimozide-increased zif-268 mRNA in the striatum and NAc core and GAD65 mRNA in the striatum and SNr. In contrast, SCH58261 did not influence vGluT2 mRNA in STN. The present study suggests an importance of the striato-subthalamo-nigro-thalamic circuit in neuroleptic-induced TJMs. The tremorolytic effect of A_2A receptor blockade seems to involve this circuit bypassing, however, STN.

震颤是帕金森病 (PD) 的运动症状之一，也存在于安定药引起的帕金森病中。震颤下颌运动 (TJMs) 被认为是一种经过充分验证的 PD 静息震颤啮齿动物模型。TJMs 可由典型的抗精神病药物诱导，并且已知可被不同的药物减少，包括腺苷 A _2A受体拮抗剂。本研究的目的是在亚慢性匹莫齐特诱导的TJMs 中寻找与选择性 A _{2A受体拮抗剂 SCH58261 的震颤作用有关的脑结构。}除了 TJMs，我们在相同的动物中评估了 zif -268 mRNA（神经元反应标记）的表达，以及谷氨酸脱羧酶 65-kDa 异构体（GAD65) 和囊泡谷氨酸转运蛋白 1 和 2 ( vGluT1/2 ) 在选定的脑结构中，分别作为 GABA 能神经元和谷氨酸能神经元的标志物。我们发现 SCH58261 减少了匹莫齐特诱导的 TJM。Pimozide 增加了纹状体、伏隔核 (NAc) 核心和黑质网状部 (SNr) 中的zif-268 mRNA 水平。此外，它增加了纹状体中的GAD65 mRNA 和信噪比，以及丘脑底核 (STN) 中的vGluT2 mRNA 水平。发现 zif -268、GAD65和vGluT2 mRNA 与 TJM之间呈正相关。SCH58261 逆转了纹状体和 NAc 核心中匹莫齐特增加的 zif -268 mRNA 和纹状体中的GAD65 mRNA 和信噪比。相反，SCH58261 不影响STN 中的vGluT2 mRNA。本研究表明纹状体-底丘脑-黑质-丘脑回路在安定药诱导的 TJM 中的重要性。然而，A _2A受体阻滞剂的震颤作用似乎涉及绕过 STN 的该电路。