Radja F, Descarries L, Dewar K M, Reader T A
Département de physiologie, Faculté de médecine, Université de Montréal, Qué, Canada.
Brain Res. 1993 Mar 26;606(2):273-85. doi: 10.1016/0006-8993(93)90995-y.
Neonatal destruction of nigrostriatal dopamine neurons by cerebroventricular injection of 6-hydroxydopamine (6-OHDA) results in a serotonin (5-HT) hyperinnervation of the rostral neostriatum in adult rat. Quantitative ligand-binding autoradiography was used to compare the density of various 5-HT receptor subtypes in the adult brain of control and neonatally 6-OHDA-lesioned rats. 5-HT1A, 5-HT1B, 5HT1nonAB and 5-HT2 sites were labeled with [3H]8-OH-DPAT, [125I]cyanopindolol, [3H]5-HT and [125I]DOI, respectively, and measured in the rostral and caudal halves of neostriatum and selected forebrain or midbrain regions. 5-HT1A binding, measured after 6 months, was unchanged in all regions examined including the dorsal raphe nucleus. Three months after the lesion, 5-HT1B binding was increased throughout the neostriatum (30%), but also in the substantia nigra (50%) and globus pallidus (30%), suggesting an up-regulation and an increased axonal transport of these receptors in neostriatal projection neurons. 5-HT1nonAB binding was also increased throughout the neostriatum (40%) and in the substantia nigra (50%), but unchanged in the globus pallidus, as if this up-regulation preferentially involved striatonigral as opposed to striatopallidal neurons. 5-HT2 binding showed an even greater increase (60%), which was restricted to the rostral half of neostriatum and also seemed imputable to an up-regulation as heteroreceptors. Even though the exact cause(s) of these receptor increases could not be determined, their anatomical distribution suggested that they were somehow related to the initial dopamine denervation in the case of the 5-HT1B and 5-HT1nonAB receptors, and more tightly linked to the 5-HT hyperinnervation in the case of the 5-HT2 receptors. Such receptor changes could participate in adaptive mechanisms implicating other transmitters and behavioral disturbances observed in this particular experimental model. Interestingly, they could also account for an enhancement of neostriatal 5-HT function even in a condition where extracellular levels of 5-HT apparently remain normal because of increased uptake.
通过脑室内注射6-羟基多巴胺（6-OHDA）对新生大鼠黑质纹状体多巴胺神经元进行破坏，会导致成年大鼠吻侧新纹状体出现5-羟色胺（5-HT）超神经支配。采用定量配体结合放射自显影术，比较对照大鼠和新生期接受6-OHDA损伤的大鼠成年大脑中各种5-HT受体亚型的密度。分别用[3H]8-OH-DPAT、[125I]氰吲哚洛尔、[3H]5-HT和[125I]DOI标记5-HT1A、5-HT1B、5HT1nonAB和5-HT2位点，并在新纹状体的吻侧和尾侧半区以及选定的前脑或中脑区域进行测量。6个月后测量的5-HT1A结合在所有检查区域（包括背侧中缝核）均未改变。损伤3个月后，整个新纹状体的5-HT1B结合增加（30%），黑质（50%）和苍白球（30%）也增加，这表明这些受体在新纹状体投射神经元中上调且轴突运输增加。整个新纹状体的5-HT1nonAB结合也增加（40%），黑质增加（50%），但苍白球未改变，似乎这种上调主要涉及纹状体黑质神经元而非纹状体苍白球神经元。5-HT2结合增加更为显著（60%），仅限于新纹状体的吻侧半区，似乎也是由于作为异受体的上调所致。尽管无法确定这些受体增加的确切原因，但其解剖分布表明，对于5-HT1B和5-HT1nonAB受体，它们在某种程度上与最初的多巴胺去神经支配有关，而对于5-HT2受体，则与5-HT超神经支配联系更为紧密。这种受体变化可能参与了涉及其他递质的适应性机制以及在此特定实验模型中观察到的行为障碍。有趣的是，即使在由于摄取增加导致细胞外5-HT水平明显保持正常的情况下，它们也可能解释新纹状体5-HT功能的增强。
