Bannon M J, Elliott P J, Alpert J E, Goedert M, Iversen S D, Iversen L L
Nature. 1983;306(5945):791-2. doi: 10.1038/306791a0.
The dopamine (DA) innervation to the forebrain arises from subpopulations of midbrain DA neurones broadly classified as nigrostriatal, mesolimbic and mesocortical. Significant differences in the autoregulatory mechanisms and neuronal inputs of these DA pathways may account for their differences in physiological and pharmacological responsiveness. For example, footshock stress can activate rat mesocortical DA cells but does not alter nigrostriatal DA turnover, while also decreasing substance P (SP) concentrations in the midbrain interpeduncular nucleus and in the adjacent ventral tegmental area (VTA), but not in the substantia nigra (SN). This suggested that the activation of the SP input to the VTA may mediate activation of certain DA systems by footshock stress; behavioural studies also had suggested an excitatory effect of SP on DA cells in the VTA. SP antagonists now available are neurotoxic and of questionable efficacy, we therefore used monoclonal antibody against SP. Antibody microinjected into the VTA prevented normal footshock-induced activation of mesocortical DA neurones, suggesting mediation by SP input to the VTA. The in vivo application of antibodies may prove valuable in studies of neuropeptides in the central nervous system (CNS).
中脑多巴胺（DA）能神经纤维向大脑前部的投射起源于中脑DA神经元的不同亚群，大致可分为黑质纹状体、中脑边缘和中脑皮质通路。这些DA通路在自身调节机制和神经元输入方面存在显著差异，这可能解释了它们在生理和药理反应性上的差异。例如，足部电击应激可激活大鼠中脑皮质DA细胞，但不改变黑质纹状体DA的更新率，同时还可降低中脑脚间核和邻近的腹侧被盖区（VTA）中的P物质（SP）浓度，但不影响黑质（SN）中的浓度。这表明，SP输入到VTA的激活可能介导了足部电击应激对某些DA系统的激活；行为学研究也表明SP对VTA中的DA细胞有兴奋作用。目前可用的SP拮抗剂具有神经毒性且疗效存疑，因此我们使用了抗SP单克隆抗体。将抗体微量注射到VTA中可阻止正常足部电击诱导的中脑皮质DA神经元的激活，提示VTA的SP输入起介导作用。抗体在体内的应用可能在中枢神经系统（CNS）神经肽的研究中具有重要价值。
