Murrin L C, Roth R H
Neuropharmacology. 1987 Jun;26(6):591-5. doi: 10.1016/0028-3908(87)90152-3.
The role of dopamine autoreceptors on nerve terminals in controlling the activity of tyrosine hydroxylase in the striatum was examined using a model involving supramaximal electrical stimulation of the nigro-neostriatal fibers and accumulation of 3,4-dihydroxyphenylalanine (DOPA) as a measure of the activity of tyrosine hydroxylase in vivo. In this way effects of drugs on impulse flow in these neurons could be negated and the effects on dopamine autoreceptors evaluated. Electrical stimulation, haloperidol, pimozide and clozapine increased the activity of tyrosine hydroxylase in vivo while trivastal, a dopamine agonist, had no significant effect. Combination of electrical stimulation with haloperidol or pimozide produced an additive effect on the activity of tyrosine hydroxylase, consistent with blockade of autoreceptors on nerve terminals. The combination of stimulation with clozapine (a drug shown to have minimal blocking action on autoreceptors in this model) produced an effect equivalent to stimulation alone, consistent with a lack of effect on autoreceptors. Trivastal reduced the effect of electrical stimulation, indicating a stimulatory action on dopamine autoreceptors on nerve terminals. These data are consistent with the theory of regulation of the activity of tyrosine hydroxylase in dopaminergic nerve terminals of the striatum by means of dopamine autoreceptors.
利用一种模型研究了神经末梢上多巴胺自身受体在控制纹状体中酪氨酸羟化酶活性方面的作用，该模型涉及对黑质 - 新纹状体纤维进行超强电刺激，并将3,4 - 二羟基苯丙氨酸（DOPA）的积累作为体内酪氨酸羟化酶活性的一种衡量指标。通过这种方式，可以消除药物对这些神经元冲动流的影响，并评估其对多巴胺自身受体的作用。电刺激、氟哌啶醇、匹莫齐特和氯氮平可增加体内酪氨酸羟化酶的活性，而多巴胺激动剂曲伐沙星则无显著影响。电刺激与氟哌啶醇或匹莫齐特联合使用对酪氨酸羟化酶的活性产生相加作用，这与神经末梢自身受体被阻断一致。刺激与氯氮平（在该模型中显示对自身受体具有最小阻断作用的药物）联合使用产生的效果与单独刺激相当，这与对自身受体无影响一致。曲伐沙星降低了电刺激的效果，表明其对神经末梢上的多巴胺自身受体具有刺激作用。这些数据与通过多巴胺自身受体调节纹状体多巴胺能神经末梢中酪氨酸羟化酶活性的理论一致。
