Dean Brian, Bradbury Robyn, Copolov David Leon
The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia.
Biol Psychiatry. 2003 Apr 1;53(7):585-92. doi: 10.1016/s0006-3223(02)01545-7.
This study investigated if changes in pre-synaptic markers on dopaminergic neurons (dopamine transporter [DAT], tyrosine hydroxylase [TH]) were present in the caudate from subjects with schizophrenia who had Delta(9)(-)tetrahydrocannabinol (THC) in their blood at autopsy. These changes were posited because animal studies show that treatment with THC decreases dopamine uptake and TH in the striatum.
Studies utilized caudate, obtained postmortem, from 14 schizophrenic and 14 control subjects. [(3)H]mazindol binding to caudate, measured using autoradiography, was taken as a measure of DAT; TH levels were estimated using an antihuman TH antibody and Western blotting.
There was decreased [(3)H]mazindol binding to DAT in the caudate from the schizophrenic subjects with no detectable blood THC levels (THC(-)) compared with THC(-) control subjects (mean +/- SEM: 240 +/- 19 vs. 296 +/- 14 fmol/mg estimated tissue equivalents, p =.01). There were no significant differences between levels of DAT in the caudate from schizophrenic and control subjects that had THC in their blood. Tyrosine hydroxylase was not different in any diagnostic cohort.
Our data suggests that DAT is decreased in the caudate from THC(-) subjects with schizophrenia, a change that may be reversed by ingesting THC from cannabis.
本研究调查了尸检时血液中含有Δ⁹-四氢大麻酚（THC）的精神分裂症患者尾状核中多巴胺能神经元上突触前标志物（多巴胺转运体[DAT]、酪氨酸羟化酶[TH]）是否发生变化。提出这些变化是因为动物研究表明，用THC治疗会降低纹状体中的多巴胺摄取和TH。
研究使用了14例精神分裂症患者和14例对照者死后获取的尾状核。用放射自显影法测量的[³H]麦角吲哚与尾状核的结合被用作DAT的指标；使用抗人TH抗体和蛋白质印迹法估计TH水平。
与THC（-）对照者相比，血液中未检测到THC水平（THC（-））的精神分裂症患者尾状核中[³H]麦角吲哚与DAT的结合减少（平均±标准误：240±19 vs. 296±14 fmol/mg估计组织当量，p = 0.01）。血液中含有THC的精神分裂症患者和对照者尾状核中DAT水平无显著差异。任何诊断队列中的酪氨酸羟化酶均无差异。
我们的数据表明，THC（-）精神分裂症患者尾状核中的DAT减少，摄入大麻中的THC可能会逆转这一变化。
