Koeltzow T E, Xu M, Cooper D C, Hu X T, Tonegawa S, Wolf M E, White F J
Department of Neuroscience, Finch University of Health Sciences, Chicago Medical School, North Chicago, Illinois 60064-3095, USA.
J Neurosci. 1998 Mar 15;18(6):2231-8. doi: 10.1523/JNEUROSCI.18-06-02231.1998.
Dopamine (DA) autoreceptors expressed along the somatodendritic extent of midbrain DA neurons modulate impulse activity, whereas those expressed at DA nerve terminals regulate both DA synthesis and release. Considerable evidence has indicated that these DA autoreceptors are of the D2 subtype of DA receptors. However, many pharmacological studies have suggested an autoreceptor role for the DA D3 receptor. This possibility was tested with mice lacking the D3 receptor as a result of gene targeting. The basal firing rates of DA neurons within both the substantia nigra and ventral tegmental area were not different in D3 receptor mutant and wild-type mice. The putative D3 receptor-selective agonist R(+)-trans-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin+ ++-9-ol (PD 128907) was equipotent at inhibiting the activity of both populations of midbrain DA neurons in the two groups of mice. In the gamma-butyrolactone (GBL) model of DA autoreceptor function, mutant and wild-type mice were identical with respect to striatal DA synthesis and its suppression by PD 128907. In vivo microdialysis studies of DA release in ventral striatum revealed higher basal levels of extracellular DA in mutant mice but similar inhibitory effects of PD 128907 in mutant and wild-type mice. These results suggest that the effects of PD 128907 on dopamine cell function reflect stimulation of D2 as opposed to D3 receptors. Although D3 receptors do not seem to be significantly involved in DA autoreceptor function, they may participate in postsynaptically activated short-loop feedback modulation of DA release.
沿中脑多巴胺（DA）神经元的树突体表达的DA自身受体调节冲动活动，而在DA神经末梢表达的自身受体则调节DA的合成和释放。大量证据表明，这些DA自身受体属于DA受体的D2亚型。然而，许多药理学研究表明DA D3受体具有自身受体作用。通过基因靶向产生的缺乏D3受体的小鼠对这一可能性进行了测试。黑质和腹侧被盖区内DA神经元的基础放电率在D3受体突变小鼠和野生型小鼠中并无差异。假定的D3受体选择性激动剂R（+）-反式-3,4,4a,10b-四氢-4-丙基-2H,5H-（1）苯并吡喃并（4,3-b）-1,4-恶嗪-9-醇（PD 128907）在抑制两组小鼠中脑DA神经元群的活性方面效力相当。在DA自身受体功能的γ-丁内酯（GBL）模型中，突变小鼠和野生型小鼠在纹状体DA合成及其被PD 128907抑制方面表现相同。对腹侧纹状体中DA释放的体内微透析研究显示，突变小鼠细胞外DA的基础水平较高，但PD 128907对突变小鼠和野生型小鼠的抑制作用相似。这些结果表明，PD 128907对多巴胺细胞功能的影响反映的是对D2受体而非D3受体的刺激。虽然D3受体似乎未显著参与DA自身受体功能，但它们可能参与DA释放的突触后激活短环反馈调节。
