Evidence that systemically administered dopamine antagonists activate dopamine neuron firing primarily by blockade of somatodendritic autoreceptors.
Evidence that systemically administered dopamine antagonists activate dopamine neuron firing primarily by blockade of somatodendritic autoreceptors.
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发表时间：
1994-12
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通讯作者：
M. L. Pucak;A. Grace
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作者：
M. L. Pucak;A. Grace
多巴胺拮抗剂的全身给药增加了黑质中一些多巴胺神经元的活性，这种作用被认为是通过两种潜在的机制发生的：1）局部阻断多巴胺作用于体树突自受体或2）阻断纹状体中突触后靶点上的受体，导致长环反馈调制。几项研究提供的证据表明，主要的影响是通过纹状体黑质反馈。在这项研究中，我们测试了后一种模型，通过比较消除纹状体黑质反馈后，多巴胺神经元激活的多巴胺拮抗剂的全身给药的行动。氟哌啶醇或多巴胺D2特异性拮抗剂舒必利的全身给药引起许多多巴胺神经元的放电率显着增加记录在完整的大鼠和大鼠的纹状体黑质投射半切。记录在半切大鼠多巴胺细胞没有表现出一致的差异，无论是在兴奋的细胞的比例或拮抗剂管理所产生的兴奋的幅度。与拮抗剂给药发生的多巴胺细胞兴奋的幅度是依赖于记录的细胞的自发放电率，与慢放电神经元一般表现出最大的兴奋性反应。这些结果提供了证据表明，纹状体中多巴胺神经元的阻断不是全身给予多巴胺拮抗剂兴奋多巴胺神经元的主要机制。因此，多巴胺拮抗剂最有可能增加多巴胺细胞放电率通过阻断体树突自身受体，这表明细胞的基础活动部分依赖于黑质内的树突释放的多巴胺。
Systemic administration of dopamine antagonists increases the activity of some dopamine neurons in the substantia nigra, and this effect is thought to occur through two potential mechanisms: 1) local blockade of dopamine acting at somatodendritic autoreceptors or 2) blockade of receptors on postsynaptic targets in the striatum, resulting in long-loop feedback modulation. Several studies have provided evidence that the major influence is via striatonigral feedback. In this study, we tested the latter model by comparing the actions of systemically administered dopamine antagonists on dopamine neuron activation after removing striatonigral feedback. Systemic administration of either haloperidol or of the dopamine D2-specific antagonist sulpiride caused significant increases in the firing rate of many dopamine neurons recorded both in intact rats and in rats with hemisection of the striatonigral projection. Dopamine cells recorded in hemisected rats did not show consistent differences in either the proportion of cells excited or in the magnitude of the excitation produced by antagonist administration. The magnitude of dopamine cell excitation occurring with antagonist administration was dependent on the spontaneous firing rate of the recorded cell, with slow-firing neurons generally exhibiting the largest excitatory responses. These results provide evidence that blockade of dopamine neurons in the striatum is not the primary mechanism by which systemically administered dopamine antagonists excite dopamine neurons. Thus, dopamine antagonists most likely increase dopamine cell firing rate by blockade of somatodendritic autoreceptors, suggesting that the basal activity of the cells is dependent in part on dendritically released dopamine within the substantia nigra.