Seeman P, Bzowej N H, Guan H C, Bergeron C, Reynolds G P, Bird E D, Riederer P, Jellinger K, Tourtellotte W W
Department of Pharmacology, University of Toronto, Canada.
Neuropsychopharmacology. 1987 Dec;1(1):5-15. doi: 10.1016/0893-133x(87)90004-2.
Because dopamine D2 receptors are known to be elevated in schizophrenic brain striata, this study examined whether a similar dopamine receptor elevation occurred in other diseases including neuroleptic-treated Alzheimer's and Huntington's diseases. The average D1 density in postmortem striata from Alzheimer's patients was 17.6 +/- 0.1 pmol/g, similar to an age-matched control density of 16.6 +/- 0.4 pmol/g. The average D1 density in schizophrenia patients was 19.0 +/- 0.6 pmol/g, similar to the age-matched control density of 17.9 +/- 0.6 pmol/g. In Parkinson's disease patients, however, the D1 receptor density was elevated, with values of 22.8 +/- 1.2 pmol/g (in patients not receiving L-DOPA) and 19.6 +/- 1.5 pmol/g (in patients receiving L-DOPA) compared to the age-matched control density of 16.0 +/- 0.4 pmol/g. The D2 receptors in Alzheimer's striata averaged 13.4 +/- 0.6 pmol/g (in patients who had not received neuroleptics), almost identical to the control density of 12.7 +/- 0.3 pmol/g. The average D2 density in neuroleptic-treated Alzheimer's striata was 16.7 +/- 0.7 pmol/g, an elevation of 31%, the individual values of which had a normal distribution. In Parkinson's disease patients, the D2 densities were elevated in tissues from patients not receiving L-DOPA (19.9 +/- 1.5 pmol/g in putamen and 14.8 +/- 1.2 pmol/g in striatum) compared to the age-matched control values of 13.0 +/- 0.4 pmol/g and 12.6 +/- 0.3 pmol/g, respectively. In Huntington's disease patients, the D2 density averaged 7.5 +/- 0.4 pmol/g in patients who had not received neuroleptics, but was 10.3 +/- 0.6 pmol/g in those who had. Although all of the D1 and D2 densities in each of the above diseases and subgroups revealed a normal distribution pattern, the D2 densities in schizophrenia displayed a bimodal distribution pattern, with 48 striata having a mode at 14 pmol/g, and the other 44 striata having a mode at 26 pmol/g. Thus, compared to the neuroleptic-induced and unimodal elevations in D2 of 31% in Alzheimer's disease and 37% in Huntington's disease, the schizophrenic striata with a mode of 26 pmol/g (105% above control) appear to contain more D2 receptors than can be accounted for by the neuroleptic administration alone.
由于已知多巴胺D2受体在精神分裂症患者的脑纹状体中升高,本研究调查了在包括接受抗精神病药物治疗的阿尔茨海默病和亨廷顿病在内的其他疾病中是否也会出现类似的多巴胺受体升高情况。阿尔茨海默病患者死后纹状体中的D1平均密度为17.6±0.1 pmol/g,与年龄匹配的对照组密度16.6±0.4 pmol/g相似。精神分裂症患者的D1平均密度为19.0±0.6 pmol/g,与年龄匹配的对照组密度17.9±0.6 pmol/g相似。然而,在帕金森病患者中,D1受体密度升高,未接受左旋多巴治疗的患者的值为22.8±1.2 pmol/g,接受左旋多巴治疗的患者的值为19.6±1.5 pmol/g,而年龄匹配的对照组密度为16.0±0.4 pmol/g。未接受抗精神病药物治疗的阿尔茨海默病患者纹状体中的D2受体平均为13.4±0.6 pmol/g,几乎与对照组密度12.7±0.3 pmol/g相同。接受抗精神病药物治疗的阿尔茨海默病患者纹状体中的D2平均密度为16.7±0.7 pmol/g,升高了31%,其个体值呈正态分布。在帕金森病患者中,未接受左旋多巴治疗的患者组织中的D2密度升高(壳核中为19.9±1.5 pmol/g,纹状体中为14.8±1.2 pmol/g),而年龄匹配的对照组值分别为13.0±0.4 pmol/g和12.6±0.3 pmol/g。在未接受抗精神病药物治疗的亨廷顿病患者中,D2密度平均为7.5±0.4 pmol/g,但接受过抗精神病药物治疗的患者中为10.3±0.6 pmol/g。尽管上述每种疾病及其亚组中的所有D1和D2密度均呈现正态分布模式,但精神分裂症患者的D2密度呈现双峰分布模式,48个纹状体的众数为14 pmol/g,另外44个纹状体的众数为26 pmol/g。因此,与抗精神病药物诱导的阿尔茨海默病中D2升高31%和亨廷顿病中升高37%的单峰情况相比,众数为26 pmol/g(比对照组高105%)的精神分裂症纹状体似乎含有比仅由抗精神病药物给药所能解释的更多的D2受体。