Strömberg I, Bickford-Wimer P
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Brain Res. 1991 Nov 15;564(2):279-85. doi: 10.1016/0006-8993(91)91464-c.
Electrophysiological recordings were performed on caudate neurons in rats with dopamine (DA) depleted striatum in combination with pertussis toxin (PT) lesions. Pertussis toxin inactivates the G protein coupled to D2 receptors. DA depletions were performed by unilateral injections of 6-hydroxydopamine (6-OHDA). After the 6-OHDA lesion, rats were challenged with low doses of apomorphine. When a double peak rotational pattern was stable over repeated rotational tests, PT was injected into striatum ipsilateral to the DA depleted side. Two days after the PT injections extracellular recordings with local applications of the D1 agonist SKF 38393 and the D2 agonist N-0437 were performed. Spontaneous firing rates, measured before drug application, were elevated in animals with both 6-OHDA and 6-OHDA/PT combination of lesions. In rats with only 6-OHDA lesions, a supersensitivity to N-0437 was observed, while no significant change in response to the D1 agonist was detected. Recordings from caudate neurons in rats with a combination of 6-OHDA and PT resulted in no response to the D2 agonist. However, a subsensitivity to the D1 agonist was detected and only 60% of neurons were inhibited by SKF 38393. Taken together, these data suggest an interaction between the D1 and D2 receptors, which is revealed only after an upregulation of the D2 receptors and subsequent blockade of D2 mediated effects.
在多巴胺（DA）耗尽的纹状体大鼠中，结合百日咳毒素（PT）损伤对尾状核神经元进行电生理记录。百日咳毒素使与D2受体偶联的G蛋白失活。通过单侧注射6-羟基多巴胺（6-OHDA）来实现DA耗尽。在6-OHDA损伤后，用低剂量阿扑吗啡对大鼠进行激发试验。当在重复的旋转试验中双峰旋转模式稳定时，将PT注射到DA耗尽侧同侧的纹状体中。PT注射两天后，在局部应用D1激动剂SKF 38393和D2激动剂N-0437的情况下进行细胞外记录。在6-OHDA损伤组以及6-OHDA/PT联合损伤组动物中，药物应用前测量的自发放电率均升高。在仅6-OHDA损伤的大鼠中，观察到对N-0437超敏，而对D1激动剂的反应未检测到显著变化。在6-OHDA和PT联合损伤的大鼠中，尾状核神经元记录结果显示对D2激动剂无反应。然而检测到对D1激动剂存在低敏，并且只有60%的神经元被SKF 38393抑制。综上所述，这些数据表明D1和D2受体之间存在相互作用，这种相互作用仅在D2受体上调以及随后D2介导的效应被阻断后才显现出来。
