Crow T J, Johnstone E C, Deakin J F, Longden A
Lancet. 1976 Sep 11;2(7985):563-6. doi: 10.1016/s0140-6736(76)91807-9.
The antipsychotic actions and extra-pyramidal side-effects of neuroleptic drugs are strongly correlated with their ability to block central dopaminergic transmission. It is argued that the former are more closely related to actions on dopaminergic mechanisms in the "mesolimbic dopamine" system, and the latter to similar actions in the striatum. Although the amphetamine psychosis closely resembles paranoid schizophrenia and may be due to excess dopamine release, clinical, biochemical, and endocrine studies suggest that dopaminergic overactivity is not a necessary concomitant of schizophrenic illnesses. It is suggested that the primary defect in schizophrenia does not lie in the dopamine neuron. It remains to be excluded that the receptors, particularly in the mesolimbic dopamine areas, become supersensitive, or that there is a deficit in a system which normally acts in antiagonism to the to the mesolimbic dopamine system.
抗精神病药物的抗精神病作用和锥体外系副作用与其阻断中枢多巴胺能传递的能力密切相关。有人认为,前者与对“中脑边缘多巴胺”系统中多巴胺能机制的作用关系更为密切,而后者与纹状体中的类似作用有关。虽然苯丙胺精神病与偏执型精神分裂症极为相似,可能是由于多巴胺释放过多所致,但临床、生化和内分泌研究表明,多巴胺能活动过度并非精神分裂症的必然伴随症状。有人提出,精神分裂症的主要缺陷并不在于多巴胺神经元。仍有待排除的是,受体,尤其是中脑边缘多巴胺区域的受体变得超敏,或者在一个通常与中脑边缘多巴胺系统起拮抗作用的系统中存在缺陷。