Joyce J N, Shane A, Lexow N, Winokur A, Casanova M F, Kleinman J E
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104-6141.
Neuropsychopharmacology. 1993 Jun;8(4):315-36. doi: 10.1038/npp.1993.32.
Serotonin (5-HT) uptake sites were mapped by autoradiographic means with [3H]cyano-imipramine ([3H]CN-IMI), the 5-HT1A receptor with [3H]8-hydroxy-2-[di-n-propyl-amino]tetralin ([3H]8-OH-DPAT), and the 5-HT2 receptor with both [3H]ketanserin and [125I]lysergic acid diethylamide ([125I]LSD) in eight nonneurologic controls and 10 cases with a diagnosis of schizophrenia. In the striatum, there was a marked heterogeneous patterning of 5-HT uptake sites that corresponded to the striosomal/matrix compartmentalization of the striatum. This organization was not matched with an equally heterogeneous pattern of either 5-HT2 or 5-HT1A receptors. For the isocortex, a general organizational scheme was observed with the 5-HT1A receptor expression high in the external laminae and deep laminae, but 5-HT2 receptor expression was higher in the internal laminae. There was a laminar distribution of 5-HT uptake sites that approximated the combined distributions of the 5-HT1A receptor and the 5-HT2 receptor. In the parahippocampal gyrus and hippocampus, the distribution of 5-HT uptake sites was complementary to the distribution of 5-HT1A and 5-HT2 receptors. In schizophrenic cases, there was a large increase in the number and altered striosomal/matrix organization of 5-HT uptake sites in the striatum. There was also an increase in the numbers of 5-HT2 receptors in the nucleus accumbens and ventral putamen of the schizophrenics. The number of 5-HT1A receptors was not modified. There was a marked reduction in 5-HT uptake sites in the external and middle laminae of the anterior cingulate, frontal cortex, and posterior cingulate, and no changes were observed in the motor cortex, temporal cortex, or hippocampus. Increased numbers of 5-HT1A receptors were found in the posterior cingulate, motor cortex, and hippocampus. Serotonin2 receptors were substantially elevated in the posterior cingulate, temporal cortex, and hippocampus, but not in the frontal, anterior cingulate, or motor cortices. Examination of the temporal lobe and hippocampus of a group of nonschizophrenic suicides (n = 8) indicated the alterations in 5-HT system in the limbic regions of the striatum, the limbic cortex, and hippocampus of the schizophrenic cases may be disease specific.
采用放射自显影法,用[3H]氰米帕明([3H]CN-IMI)标记5-羟色胺(5-HT)摄取位点,用[3H]8-羟基-2-[二正丙基氨基]四氢萘([3H]8-OH-DPAT)标记5-HT1A受体,并用[3H]酮色林和[125I]麦角酸二乙酰胺([125I]LSD)标记5-HT2受体,对8名非神经系统对照者和10例精神分裂症患者进行研究。在纹状体中,5-HT摄取位点呈现出明显的异质性分布模式,与纹状体的纹状体小体/基质分区相对应。这种组织模式与5-HT2或5-HT1A受体的同样异质性模式并不匹配。在同型皮质中,观察到一种一般的组织模式,即5-HT1A受体在外层和深层表达较高,但5-HT2受体在内层表达较高。5-HT摄取位点呈层状分布,近似于5-HT1A受体和5-HT2受体的联合分布。在海马旁回和海马中,5-HT摄取位点的分布与5-HT1A和5-HT2受体的分布互补。在精神分裂症患者中,纹状体中5-HT摄取位点的数量大幅增加,且纹状体小体/基质组织发生改变。精神分裂症患者伏隔核和腹侧壳核中的5-HT2受体数量也增加。5-HT1A受体的数量未改变。前扣带回、额叶皮质和后扣带回的外层和中层中5-HT摄取位点明显减少,而运动皮质、颞叶皮质或海马中未观察到变化。在后扣带回、运动皮质和海马中发现5-HT1A受体数量增加。5-HT2受体在后扣带回、颞叶皮质和海马中显著升高,但在额叶、前扣带回或运动皮质中未升高。对一组非精神分裂症自杀者(n = 8)的颞叶和海马进行检查表明,精神分裂症患者纹状体边缘区、边缘皮质和海马中5-HT系统的改变可能是疾病特异性的。