Seeman Philip, Weinshenker David, Quirion Remi, Srivastava Lalit K, Bhardwaj Sanjeev K, Grandy David K, Premont Richard T, Sotnikova Tatyana D, Boksa Patricia, El-Ghundi Mufida, O'dowd Brian F, George Susan R, Perreault Melissa L, Männistö Pekka T, Robinson Siobhan, Palmiter Richard D, Tallerico Teresa
Pharmacology Department, Medical Science Building, Room 4344, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8.
Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3513-8. doi: 10.1073/pnas.0409766102. Epub 2005 Feb 16.
Dopamine supersensitivity occurs in schizophrenia and other psychoses, and after hippocampal lesions, antipsychotics, ethanol, amphetamine, phencyclidine, gene knockouts of Dbh (dopamine beta-hydroxylase), Drd4 receptors, Gprk6 (G protein-coupled receptor kinase 6), Comt (catechol-O-methyltransferase), or Th-/-, DbhTh/+ (tyrosine hydroxylase), and in rats born by Cesarean-section. The functional state of D2, or the high-affinity state for dopamine (D2High), was measured in these supersensitive animal brain striata. Increased levels and higher proportions (40-900%) for D2High were found in all these tissues. If many types of brain impairment cause dopamine behavioral supersensitivity and a common increase in D2High states, it suggests that there are many pathways to psychosis, any one of which can be disrupted.
多巴胺超敏反应发生于精神分裂症和其他精神病中，以及海马体损伤后、使用抗精神病药物后、乙醇、苯丙胺、苯环利定、多巴胺β-羟化酶（Dbh）基因敲除、多巴胺D4受体（Drd4）基因敲除、G蛋白偶联受体激酶6（Gprk6）基因敲除、儿茶酚-O-甲基转移酶（Comt）基因敲除、酪氨酸羟化酶（Th）基因敲除/或DbhTh/+杂合子动物，以及剖宫产出生的大鼠中。在这些超敏动物的脑纹状体中测量了D2的功能状态，即多巴胺的高亲和力状态（D2High）。在所有这些组织中均发现D2High水平升高且比例更高（40 - 900%）。如果多种类型的脑损伤会导致多巴胺行为超敏反应以及D2High状态普遍增加，这表明存在许多通往精神病的途径，其中任何一条途径都可能被破坏。
