The dopamine hypothesis proposes that there is a hypodopaminergic state in the prefrontal cortex and a hyperdopaminergic state in the striatum of patients with schizophrenia. Evidence suggests the hyperdopaminergic state in the striatum is due to synaptic dopamine elevation, particularly in the dorsal striatum. However, the molecular mechanisms causing disrupted dopaminergic function in schizophrenia remains unclear. We postulated that the dopamine transporter (DAT), which regulates intra-synaptic dopamine concentrations by transporting dopamine from the synaptic cleft into the pre-synaptic neuron, could be involved in dopaminergic dysfunction in schizophrenia. Therefore, we measured levels of DAT in the cortex and striatum from patients with schizophrenia and controls using postmortem human brain tissue. Levels of desmethylimipramine-insensitive mazindol-sensitive [³H]mazindol binding to DAT were measured using in situ radioligand binding and autoradiography in gray matter from Brodmann’s area (BA) 10, BA 17, the dorsal striatum, and nucleus accumbens from 15 patients with schizophrenia and 15 controls. Levels of desmethylimipramine-insensitive mazindol-sensitive [³H]mazindol binding were significantly higher in BA 10 from patients with schizophrenia (p = 0.004) and significantly lower in the dorsal striatum (dorsal putamen p = 0.005; dorsal caudate p = 0.007) from those with the disorder. There were no differences in levels of desmethylimipramine-insensitive [³H]mazindol binding in BA 17 or nucleus accumbens. These data raise the possibility that high levels of DAT in BA 10 could be contributing to lower synaptic cortical dopamine, whereas lower levels of DAT could be contributing to a hyperdopaminergic state in the dorsal striatum.

多巴胺假说认为精神分裂症患者的前额叶皮层有低多巴胺能状态，纹状体有高多巴胺能状态。有证据表明纹状体中的高多巴胺能状态是由于突触多巴胺升高，特别是在背侧纹状体中。然而，导致精神分裂症的多巴胺能功能破坏的分子机制仍不清楚。我们推测，通过将多巴胺从突触间隙转移到突触前神经元中来调节突触内多巴胺浓度的多巴胺转运蛋白（DAT）可能与精神分裂症的多巴胺能功能障碍有关。因此，我们使用死后人脑组织测量了精神分裂症患者和对照患者的皮质和纹状体中DAT的水平。在15名精神分裂症患者和15名对照的Brodmann病区（BA）10，BA 17，背侧纹状体和伏隔核中，使用原位放射配体结合和放射自显影测量³ H] mazindol与DAT的结合。在患有精神分裂症的患者中，BA 10中对去甲丙咪嗪不敏感的对mazindol敏感的[ ³ H] mazindol结合水平显着更高（p  = 0.004），而在背侧纹状体中的显着较低（背侧壳核p  = 0.005；背尾状p  = 0.007）那些有障碍的人。对去甲基丙咪嗪不敏感的水平没有差异[ ³H] mazindol结合在BA 17或伏隔核中。这些数据增加了BA 10中高水平的DAT可能导致较低的突触皮质多巴胺，而较低水平的DAT可能导致背侧纹状体高多巴胺能状态的可能性。