Yasuda Kazuya, Abe Hiroshi, Koganemaru Go, Ikeda Tetsuya, Arimori Kazuhiko, Ishida Yasushi
Department of Psychiatry, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-city, Miyazaki 889-1692, Japan; Department of Pharmacy, University of Miyazaki Hospital, 5200 Kihara, Kiyotake, Miyazaki-city, Miyazaki 889-1692, Japan.
Department of Psychiatry, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-city, Miyazaki 889-1692, Japan.
Pharmacol Biochem Behav. 2015 Apr;131:1-5. doi: 10.1016/j.pbb.2015.01.012. Epub 2015 Jan 24.
Pramipexole is widely prescribed for the treatment of Parkinson's disease. This dopamine (DA) receptor agonist has a higher affinity for D3 over D2 receptors. We compared the effect of pramipexole to apomorphine, a non-specific DA receptor agonist, on the suppression of tremulous jaw movements (TJMs) in a rat model, to elucidate the possible ameliorating effect of D3 receptor activation on parkinsonian tremor.
In experiment 1, pilocarpine (4.0mg/kg) was injected into rats intraperitoneally, and the number of rapid vertical deflections of the lower jaw was counted for 20min immediately after the injection, to evaluate TJMs. TJMs were reduced by intraperitoneal administration of pramipexole (1.0mg/kg). In experiment 2, the number of TJMs was counted after the rats received intraperitoneal administration of either apomorphine (0.25, 1.0, 4.0mg/kg) or vehicle, followed by the micro-infusion of pilocarpine (50μg/1μL/side) or vehicle into the ventrolateral striatum (VLS) via implanted guide cannulae. In experiment 3, either pramipexole (0.25, 1.0, 4.0mg/kg) or vehicle was intraperitoneally administered, followed by the micro-infusion of pilocarpine or vehicle into the VLS 30min later. Pramipexole (1.0 and 4.0mg/kg) and apomorphine (1.0 and 4.0mg/kg) significantly reduced the number of TJMs induced by micro-infusion of pilocarpine into the VLS.
These findings suggest that activation of D3, as well as D2 receptors could play important roles in the suppression of parkinsonian tremor.
普拉克索被广泛用于治疗帕金森病。这种多巴胺（DA）受体激动剂对D3受体的亲和力高于D2受体。我们比较了普拉克索与非特异性DA受体激动剂阿扑吗啡对大鼠模型中震颤性下颌运动（TJMs）抑制作用的效果，以阐明D3受体激活对帕金森震颤可能的改善作用。
在实验1中，将毛果芸香碱（4.0mg/kg）腹腔注射到大鼠体内，并在注射后立即计数下颌快速垂直偏转的次数20分钟，以评估TJMs。腹腔注射普拉克索（1.0mg/kg）可减少TJMs。在实验2中，大鼠腹腔注射阿扑吗啡（0.25、1.0、4.0mg/kg）或赋形剂后，通过植入的引导套管将毛果芸香碱（50μg/1μL/侧）或赋形剂微量注入腹外侧纹状体（VLS），然后计数TJMs的次数。在实验3中，腹腔注射普拉克索（0.25、1.0、4.0mg/kg）或赋形剂，30分钟后将毛果芸香碱或赋形剂微量注入VLS。普拉克索（1.0和4.0mg/kg）和阿扑吗啡（1.0和4.0mg/kg）显著减少了向VLS微量注射毛果芸香碱诱导的TJMs次数。
这些发现表明，D3受体以及D2受体的激活在抑制帕金森震颤中可能起重要作用。
