Amphetamine sensitization of hallucinatory-like behaviors is dependent on prefrontal cortex in nonhuman primates
Amphetamine sensitization of hallucinatory-like behaviors is dependent on prefrontal cortex in nonhuman primates
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DOI：
10.1016/s0006-3223(03)00292-0
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发表时间：
2003-07-15
影响因子：
10.6
通讯作者：
Goldman-Rakic, PS
中科院分区：
文献类型：
--
作者：
Castner, SA;Goldman-Rakic, PS
背景资料：非人灵长类动物反复暴露于安非他明（AMPH）会产生慢性单胺调节障碍状态，以及由急性AMPH引起的长期行为变化（包括跟踪、“在稀薄的空气中”抓握、操纵非明显刺激和过度警觉），其方式与安非他明精神病和偏执型精神分裂症的症状明显相似。这些异常反应在历史上被称为拟精神病或幻觉样。相反，阴性症状和认知缺陷，精神分裂症的阳性症状，包括幻觉没有传统上被链接到前额叶dysfunctions.Methods：背内侧（9/8B），背外侧（46/8A），和下（45/12）部门的前额叶皮质的病变，单独或组合。病变和非病变的控制猴致敏超过6周的时间内使用的间歇性时间表递增低剂量的AMPH。结果：与对照组动物相比，急性AMPH慢性暴露后的行为反应与暴露前的反应相比。这些发现表明，灵长类动物的前额叶皮层可能是一个基板的发展的完整的行为引起的AMPH过敏，包括幻觉样行为。(C)2003生物精神病学学会。
Background: Repeated amphetamine (AMPH) exposure in nonhuman primates produces a chronic state of monoamine dysregulation and long-lasting changes in behaviors elicited by acute AMPH (including tracking, grasping "at thin air," manipulating nonapparent stimuli, and hypervigilance) in a manner that bears a marked resemblance to symptoms of both amphetamine psychosis and paranoid schizophrenia. These abnormal responses have historically been referred to as psychotomimetic or hallucinatory-like. In contrast to negative symptoms and cognitive deficits, the positive symptoms of schizophrenia including hallucinations have not traditionally been linked to prefrontal dysfunction.Methods: The dorsomedial (9/8B), dorsolateral (46/8A), and inferior (45/12) sectors of prefrontal cortex were lesioned, singly or in combination. Lesioned and non-lesioned control monkeys were sensitized over a 6-week period using an intermittent schedule of escalating low doses of AMPH. Behavioral responses to acute AMPH after chronic exposure were compared with preexposure responses.Results: Bilateral lesions of prefrontal cortex performed before subchronic AMPH suppressed the sensitization of hallucinatory-like behaviors but markedly enhanced locomotor sensitization compared with control animals.Conclusions: These findings indicate that the primate prefrontal cortex may be a substrate for the development of the full complement of behaviors elicited by AMPH sensitization, including hallucinatory-like behaviors. (C) 2003 Society of Biological Psychiatry.