Castner Stacy A, Goldman-Rakic Patricia S
Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Biol Psychiatry. 2003 Jul 15;54(2):105-10. doi: 10.1016/s0006-3223(03)00292-0.
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.
The dorsomedial (9/8B), dorsolateral (46/8A), and inferior (45/12) sectors of prefrontal cortex were lesioned, singly or in combination. Lesioned and nonlesioned 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.
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.
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.
在非人灵长类动物中反复给予苯丙胺（AMPH）会导致单胺调节紊乱的慢性状态，以及急性AMPH引发的行为出现持久变化（包括追踪、凭空抓握、操控非明显刺激和过度警觉），其方式与苯丙胺精神病和偏执型精神分裂症的症状极为相似。这些异常反应历来被称为拟精神病性或类幻觉性反应。与阴性症状和认知缺陷不同，精神分裂症的阳性症状（包括幻觉）传统上并未与前额叶功能障碍相关联。
对前额叶皮质的背内侧（9/8B）、背外侧（46/8A）和腹侧（45/12）区域进行单独或联合损伤。使用递增低剂量AMPH的间歇性给药方案，对损伤组和未损伤的对照猴进行为期6周的致敏。将慢性暴露后对急性AMPH的行为反应与暴露前的反应进行比较。
在亚慢性AMPH给药前进行双侧前额叶皮质损伤，与对照动物相比，抑制了类幻觉行为的致敏，但显著增强了运动致敏。
这些发现表明，灵长类前额叶皮质可能是AMPH致敏引发的全部行为（包括类幻觉行为）发展的基础。
