Modeling sensitization to stimulants in humans -: An [11C] raclopride/positron emission tomography study in healthy men
Modeling sensitization to stimulants in humans -: An [11C] raclopride/positron emission tomography study in healthy men
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DOI：
10.1001/archpsyc.63.12.1386
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发表时间：
2006-12-01
影响因子：
--
通讯作者：
Benkelfat, Chawki
中科院分区：
文献类型：
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作者：
Boileau, Isabelle;Dagher, Alain;Benkelfat, Chawki
背景：在动物中，反复暴露于兴奋剂药物会导致药物诱导的精神运动反应增强和多巴胺释放增加。这种被称为致敏的现象，可能使人类易受药物成瘾或药物引起的精神病的影响。一个类似的现象，被称为内源性致敏，也被认为在精神分裂症患者出现阳性症状中起作用。目的：确定健康个体在实验室有限暴露于安非他明后是否会发生行为和神经化学致敏。设计：开放标签，健康志愿者反复服用安非他明1年随访。单位：麦吉尔大学精神学系和蒙特利尔神经学研究所麦康奈尔脑成像中心。参与者：10名健康男性（平均+/- SD年龄25.8 +/- 1.8岁）。干预：在第1、3、5天给予三次单剂量安非他明（硫酸右苯丙胺，0.3 mg/kg口服）。主要结果测量：我们使用正电子发射断层扫描和[C-11] raclopride，测量了安非他明首次暴露（第1天）和第三次暴露后14天和1年的多巴胺释放。结果：初始剂量的安非他明引起了腹侧纹状体多巴胺的释放（[C-11] raclopride结合减少）。与致敏样现象一致，在第三剂量安非他明后的第14和365天，相对于初始剂量，腹侧纹状体有更大的精神运动反应和增加的多巴胺释放（[C-11] raclopride结合更大的减少），逐渐延伸到尾状体背侧和壳核。高度追求新奇的个性特征和表明冲动的自评评估预示着敏感化倾向。结论：在实验室中，健康男性可以对兴奋剂致敏。这种现象与多巴胺释放增加有关，并持续至少1年。
Context: In animals, repeated exposure to stimulant drugs leads to an enhanced drug-induced psychomotor response and increased dopamine release. This phenomenon, known as sensitization, may confer vulnerability to drug addiction or drug-induced psychosis in humans. A similar phenomenon, referred to as endogenous sensitization, is also believed to play a role in the emergence of positive symptoms in patients with schizophrenia.Objective: To determine whether behavioral and neurochemical sensitization occur in healthy individuals after limited exposure to amphetamine in the laboratory.Design: Open-label, 1-year follow-up of repeated amphetamine administration in healthy volunteers.Setting: Department of Psychiatry, McGill University, and McConnell Brain Imaging Center, Montreal Neurological Institute.Participants: Ten healthy men (mean +/- SD age, 25.8 +/- 1.8 years).Intervention: Three single doses of amphetamine (dextroamphetamine sulfate, 0.3 mg/kg by mouth) were administered on days 1, 3, and 5.Main Outcome Measures: Using positron emission tomography and [C-11] raclopride, we measured dopamine release in response to amphetamine on the first exposure (day 1) and 14 days and 1 year after the third exposure.Results: The initial dose of amphetamine caused dopamine release in the ventral striatum (a reduction in [C-11] raclopride binding). Consistent with a sensitization-like phenomenon, 14 and 365 days after the third dose of amphetamine there was a greater psychomotor response and increased dopamine release (a greater reduction in [C-11] raclopride binding), relative to the initial dose, in the ventral striatum, progressively extending to the dorsal caudate and putamen. A high novelty-seeking personality trait and self-rating assessments indicating impulsivity predicted proneness to sensitization.Conclusions: Sensitization to stimulants can be achieved in healthy men in the laboratory. This phenomenon is associated with increased dopamine release and persists for at least 1 year.