Trugman J M, Arnold W S, Touchet N, Wooten G F
Department of Neurology, University of Virginia Health Sciences Center, Charlottesville.
J Pharmacol Exp Ther. 1989 Sep;250(3):1156-60.
In rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra, the 2-deoxyglucose (2-DG) autoradiographic method of measuring regional cerebral glucose utilization (RCGU) was used to assess the effects of three systemically administered dopamine agonists: bromocriptine, pergolide and (+)-4-propyl-9-hydroxynaphoxazine (PHNO). Pergolide increased RCGU in the substantia nigra pars reticulata (SNr) ipsilateral to the lesion in a dose-dependent manner (0.04 mg/kg, up 52%; 0.4 mg/kg, up 111%), resulting in asymmetric glucose utilization on the dopamine-denervated and intact sides of the brain. Pretreatment with a selective D1 antagonist (SCH 23390, 0.5 mg/kg) blocked completely the RCGU increase elicited by pergolide (0.4 mg/kg) whereas pretreatment with a selective D2 antagonist (eticlopride, 1.0 mg/kg) only mildly attenuated this increase. The effect of drug treatments on RCGU in the entopeduncular nucleus (EP) paralleled that in the SNr. These results demonstrate that the RCGU increase in the EP and SNr after pergolide administration is dependent primarily on D1 receptor stimulation. Administration of bromocriptine and PHNO minimally altered RCGU in the ipsilateral EP and SNr and did not result in significant left/right RCGU asymmetry. Considered in the context of prior studies of selective D1 and D2 agonists, the results suggest that, in this model, the magnitude of the RCGU increase in the EP and SNr elicited by a dopamine agonist, above the modest effects produced by selective D2 stimulation, represents a measure of D1 agonist effect in vivo. The results support a nonselective D1/D2 stimulatory effect of pergolide (0.04-0.4 mg/kg) and a selective D2 action of both bromocriptine and PHNO.
在单侧黑质6-羟基多巴胺（6-OHDA）损伤的大鼠中，采用2-脱氧葡萄糖（2-DG）放射自显影法测量局部脑葡萄糖利用率（RCGU），以评估三种全身给药的多巴胺激动剂的作用：溴隐亭、培高利特和（+）-4-丙基-9-羟基萘并恶嗪（PHNO）。培高利特以剂量依赖性方式增加损伤同侧黑质网状部（SNr）的RCGU（0.04 mg/kg时，增加52%；0.4 mg/kg时，增加111%），导致大脑多巴胺去神经支配侧和完整侧的葡萄糖利用不对称。用选择性D1拮抗剂（SCH 23390，0.5 mg/kg）预处理可完全阻断培高利特（0.4 mg/kg）引起的RCGU增加，而用选择性D2拮抗剂（依托必利，1.0 mg/kg）预处理仅轻度减弱这种增加。药物治疗对豆状核内核（EP）RCGU的影响与对SNr的影响相似。这些结果表明，培高利特给药后EP和SNr中RCGU的增加主要依赖于D1受体刺激。溴隐亭和PHNO的给药对同侧EP和SNr中的RCGU影响最小，且未导致明显的左右RCGU不对称。结合先前对选择性D1和D2激动剂的研究结果来看，这些结果表明，在该模型中，如果多巴胺激动剂引起的EP和SNr中RCGU的增加幅度超过选择性D2刺激产生的适度效应，则代表体内D1激动剂效应的一种度量。结果支持培高利特（0.04 - 0.4 mg/kg）具有非选择性D1/D2刺激作用，而溴隐亭和PHNO均具有选择性D2作用。
