Ryan L J, Diana M, Young S J, Groves P M
Department of Psychiatry, University of California, San Diego, La Jolla 92093.
Exp Brain Res. 1989;77(1):161-5. doi: 10.1007/BF00250578.
The role of dopamine D1 heteroreceptors located on the axon terminals of striatonigral neurons was investigated. Local infusion of the direct acting, specific dopamine D1 agonist, R-SKF 38393, into the substantia nigra terminal field of antidromically identified neostriatal projection neurons decreased the electrical excitability of these axons. This effect was dose-dependent and could be partially reversed by subsequent infusion of the specific D1 antagonist, R-SCH 23390. In contrast, excitability was not affected by the systemic administration of SCH-23390 (0.3 and 0.6 mg/kg, iv), or the non-specific antagonist haloperidol (0.2 mg/kg, iv). Since activation of the D1 heterorecptors by R-SKF 38393 decreased excitability, the inability of these antagonists to modify excitability indicates that endogenous dopamine does not tonically activate these receptors. Systemic administration of the indirect acting agonist, amphetamine (1.0 and 5.0 mg/kg, iv) also failed to change terminal excitability suggesting that, even when unnaturally high levels of dopamine are released in the substantia nigra, endogenous dopamine does not affect neostriatal axons terminating in the substantia nigra. Thus it is unlikely that endogeneous dopamine modulates neostriatal control of the substantia nigra through these presynaptic terminal D1 heteroreceptors.
研究了位于纹状体黑质神经元轴突终末上的多巴胺D1异源受体的作用。将直接作用的特异性多巴胺D1激动剂R-SKF 38393局部注入经逆向鉴定的新纹状体投射神经元的黑质终末场，可降低这些轴突的电兴奋性。这种效应呈剂量依赖性，随后注入特异性D1拮抗剂R-SCH 23390可部分逆转。相比之下，SCH-23390（0.3和0.6mg/kg，静脉注射）或非特异性拮抗剂氟哌啶醇（0.2mg/kg，静脉注射）的全身给药对兴奋性没有影响。由于R-SKF 38393激活D1异源受体可降低兴奋性，这些拮抗剂无法改变兴奋性表明内源性多巴胺不会持续激活这些受体。间接作用激动剂苯丙胺（1.0和5.0mg/kg，静脉注射）的全身给药也未能改变终末兴奋性，这表明即使在黑质中释放出异常高水平的多巴胺时，内源性多巴胺也不会影响终止于黑质的新纹状体轴突。因此，内源性多巴胺不太可能通过这些突触前终末D1异源受体调节新纹状体对黑质的控制。
