An Juan Ji, Bae Mi-Hyun, Cho Sang Rae, Lee Soo-Hyun, Choi Seong-Hoon, Lee Bae Hwan, Shin Hee-Sup, Kim Yong Nyun, Park Kye Won, Borrelli Emiliana, Baik Ja-Hyun
Laboratory of Electrophysiology, Medical Research Center, College of Medicine, Yonsei University, Seoul 120-752, South Korea.
Mol Cell Neurosci. 2004 Apr;25(4):732-41. doi: 10.1016/j.mcn.2003.12.010.
The levels of glutamic acid decarboxylase (GAD) were strongly increased in the cortex and the striatum in dopamine D2 receptors null (D2R-/-) mice, which show a significant locomotor impairment. In this study, the effects of different GABAergic drugs on locomotor activity were analyzed in D2R-/- mice. After administering muscimol (1 mg/kg), a GABA(A) receptor agonist, the D2R-/- mice showed increased locomotor activity up to 200%. When the muscimol dose was increased (4-6 mg/kg), the D2R-/- mice exhibited seizure-like behavior, and the electroencephalographic (EEG) recordings during these behaviors showed a high amplitude rhythmic epileptiform activity in these mice. In situ hybridization showed that after injecting muscimol in the D2R-/- mice, the expression of enkephalin and immediate early gene, NGFI-A, was closely regulated with the locomotor activity regulated by GABAergic stimulation. These results suggest that the absence of D2R alters the GABAergic neurotransmission, specifically on GABA(A)-receptor mediated signaling, and stimulating the GABA(A) receptor can reverse the dysfunction of GABAergic inhibition in the motor circuits in the basal ganglia.
在表现出明显运动障碍的多巴胺D2受体缺失（D2R-/-）小鼠的皮层和纹状体中，谷氨酸脱羧酶（GAD）水平显著升高。在本研究中，分析了不同GABA能药物对D2R-/-小鼠运动活性的影响。给予GABA(A)受体激动剂蝇蕈醇（1 mg/kg）后，D2R-/-小鼠的运动活性增加高达200%。当蝇蕈醇剂量增加（4-6 mg/kg）时，D2R-/-小鼠表现出癫痫样行为，这些行为期间的脑电图（EEG）记录显示这些小鼠出现高振幅节律性癫痫样活动。原位杂交显示，在D2R-/-小鼠中注射蝇蕈醇后，脑啡肽和即刻早期基因NGFI-A的表达与GABA能刺激调节的运动活性密切相关。这些结果表明，D2R的缺失改变了GABA能神经传递，特别是对GABA(A)受体介导的信号传导，并且刺激GABA(A)受体可以逆转基底神经节运动回路中GABA能抑制的功能障碍。
