Dewar K M, Grondin L, Carli M, Lima L, Reader T A
Hôpital Louis-H. Lafontaine, Département de Psychiatrie, Montréal, Québec, Canada.
J Neurochem. 1992 Jan;58(1):250-7. doi: 10.1111/j.1471-4159.1992.tb09303.x.
The agents p-chlorophenylalanine (PCPA) and p-chloroamphetamine (PCA) deplete brain serotonin (5-HT) levels by two different mechanisms; PCPA inhibits the enzyme tryptophan hydroxylase, whereas PCA has a neurotoxic action on certain 5-HT neurons. The parameters of [3H]paroxetine binding to homogenates prepared from the cerebral cortex of rats treated with PCPA, PCA, or saline; vehicle were investigated. The tissue concentrations of 5-HT and 5-hydroxyindole-3-acetic acid (5-HIAA) were also determined by HPLC in the same brain samples. After PCPA treatment, neither the maximum binding capacity (Bmax) nor the dissociation constant (KD) of [3H]paroxetine for the 5-HT uptake recognition site differed from controls despite a substantial reduction in the concentration of 5-HT and 5-HIAA. In contrast, significant changes in both the Bmax and KD values were observed in the cerebral cortex of rats treated with PCA. Furthermore, [3H]paroxetine binding and tissue concentrations of 5-HT and 5-HIAA were measured in the following different regions of the rat brain: cingulate, parietal, and visual cortical areas; dorsal and ventral hippocampus; rostral and caudal halves of neostriatum; ventral mesencephalic tegmentum; and midbrain raphe nuclei region after administration of PCPA, PCA, or saline vehicle. There was an excellent correlation between regional 5-HT levels and specific [3H]paroxetine binding in control and PCA-treated rats although this correlation was lost after PCPA treatment. Under these conditions, the 5-HT innervation remains unchanged whereas the concentration of 5-HT and 5-HIAA is greatly reduced. Thus, [3H]paroxetine binding appears to provide a reliable marker of 5-HT innervation density within the mammalian CNS.
对氯苯丙氨酸（PCPA）和对氯苯丙胺（PCA）通过两种不同机制降低脑内5-羟色胺（5-HT）水平；PCPA抑制色氨酸羟化酶，而PCA对某些5-HT神经元具有神经毒性作用。研究了[3H]帕罗西汀与用PCPA、PCA或生理盐水（赋形剂）处理的大鼠大脑皮质匀浆结合的参数。同时，还通过高效液相色谱法测定了相同脑样本中5-HT和5-羟吲哚-3-乙酸（5-HIAA）的组织浓度。PCPA处理后，尽管5-HT和5-HIAA浓度大幅降低，但[3H]帕罗西汀对5-HT摄取识别位点的最大结合容量（Bmax）和解离常数（KD）与对照组相比均无差异。相反，在用PCA处理的大鼠大脑皮质中，观察到Bmax和KD值均有显著变化。此外，在给予PCPA、PCA或生理盐水赋形剂后，测量了大鼠脑以下不同区域的[3H]帕罗西汀结合以及5-HT和5-HIAA的组织浓度：扣带回、顶叶和视觉皮质区域；背侧和腹侧海马体；新纹状体的嘴侧和尾侧半部；腹侧中脑被盖；以及中脑缝际核区域。在对照和PCA处理的大鼠中，区域5-HT水平与[3H]帕罗西汀特异性结合之间存在良好的相关性，尽管PCPA处理后这种相关性消失。在这些条件下，5-HT神经支配保持不变，而5-HT和5-HIAA的浓度大幅降低。因此，[3H]帕罗西汀结合似乎是哺乳动物中枢神经系统内5-HT神经支配密度的可靠标志物。
