METHAMPHETAMINE-INDUCED BEHAVIORAL SENSITIZATION AND ITS IMPLICATIONS FOR RELAPSE OF SCHIZOPHRENIA
METHAMPHETAMINE-INDUCED BEHAVIORAL SENSITIZATION AND ITS IMPLICATIONS FOR RELAPSE OF SCHIZOPHRENIA
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DOI：
10.1016/0920-9964(94)90035-3
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发表时间：
1994-06-01
影响因子：
4.5
通讯作者：
UJIKE, H
中科院分区：
文献类型：
--
作者：
AKIYAMA, K;KANZAKI, A;UJIKE, H
复发的脆弱性是精神分裂症生物学中的一个核心问题。这种脆弱性背后的共同的神经机制，可以研究使用的实验模型的行为敏化诱导重复给药低剂量的甲基苯丙胺（MAP）的啮齿动物。本文从精神病性症状的发生（或发展）及其表达的不同机制出发，综述了MAP诱导的行为敏化的行为学和神经化学研究。大鼠对MAP的行为敏化的启动需要刺激多巴胺能神经元，并且可以被SCH 23390（多巴胺D1受体拮抗剂）和BMY 14802（σ受体拮抗剂）阻断。亚慢性MAP预处理诱导的行为敏化的表达有几种形式。首先，多巴胺释放从大脑多巴胺能神经元终端包含响应于MAP或可卡因，或诱发的纹状体内哇巴因输注再激发的区域增强。第二，对多巴胺D2和σ受体激动剂的行为反应增强。第三种形式涉及指示跨突触神经回路的变化，例如黑质网状部中D1受体数量的增加、对D1受体活化的电生理反应的增强、兴奋性氨基酸受体的假定作用以及MAP和应激的可重复性。虽然MAP诱导的啮齿动物行为敏化作为一个有用的动物模型，精神分裂症患者的精神病发作复发的脆弱性所涉及的机制的阐明需要进一步的研究。
Vulnerability to relapse is a central issue in the biology of schizophrenia. The common neural mechanisms underlying such vulnerability can be studied using the experimental model of behavioral sensitization induced by repeated administration of low doses of methamphetamine (MAP) to rodents. This review summarizes a series of behavioral and neurochemical studies on MAP-induced behavioral sensitization from the viewpoint that the mechanisms involved in initiation (or development) of psychotic symptoms and their expression differ. The initiation of behavioral sensitization to MAP in rats requires stimulation of dopaminergic neurons, and can be blocked by SCH 23390 (a dopamine D1-receptor antagonist) and BMY 14802 (a sigma-receptor antagonist). The expression of behavioral sensitization induced by subchronic MAP pretreatment takes several forms. First, dopamine release from the cerebral dopaminergic neuron terminal containing areas in response to either to rechallenge with MAP or cocaine, or evoked by intrastriatal ouabain infusion is enhanced. Second, the behavioral responses to dopamine D2- and sigma-receptor agonists are augmented. A third form involves changes indicative of transsynaptic neural circuits, such as increased numbers of D1 receptors in the substantia nigra pars reticulata, enhanced electrophysiological responses to D1 receptor activation, the putative role of excitatory amino acid receptors and interchangeability of MAP and stress. Although MAP-induced behavioral sensitization in rodents serves as a useful animal model, the elucidation of the mechanisms involved in the vulnerability of patients with schizophrenia to relapse of psychotic episodes requires further study.