Kondrad Robyn L, Burk Joshua A
Department of Psychology, College of William and Mary, Williamsburg, VA 23187, USA.
Psychopharmacology (Berl). 2004 Oct;175(4):436-42. doi: 10.1007/s00213-004-1857-z.
Attentional deficits are thought to be critically involved in the development of positive symptoms in schizophrenia. The present experiment tests the general hypothesis that sensitization of the mesolimbic dopaminergic system contributes to the attentional deficits in schizophrenia.
The present study assessed attentional performance following administration of an escalating amphetamine regimen and subsequent "challenge" amphetamine administration in rats.
Rats were trained to perform a two-lever sustained attention task that involved discrimination of visual signals and no signal presentation. After reaching criterion, subjects were assigned to receive escalating amphetamine or saline. Attentional performance was assessed immediately following escalating amphetamine, following "challenge" amphetamine administration (1.0 mg/kg) to amphetamine-pretreated rats, and for 3 days after the challenge session. At the end of this experiment, a dose-response study was conducted with saline-pretreated rats to confirm the appropriateness of the challenge dose.
Amphetamine-pretreated animals demonstrated a transient increase in errors on nonsignal trials following escalating amphetamine administration. The latency to press a lever was decreased during and after challenge amphetamine administration. Administration of 1.0 mg/kg amphetamine did not alter accuracy of amphetamine-pretreated animals or of saline-pretreated animals in the dose-response experiment.
Prior escalating amphetamine administration transiently disrupted attention, increasing incorrect "claims" for a signal on trials when no signal was presented. The present data support the existing literature that escalating amphetamine regimens may be useful to model the attentional deficits that contribute to the psychotic symptoms in schizophrenia.
注意力缺陷被认为在精神分裂症阳性症状的发展中起关键作用。本实验检验了一个总体假设，即中脑边缘多巴胺能系统的敏感化导致了精神分裂症中的注意力缺陷。
本研究评估了大鼠在接受递增剂量苯丙胺给药方案及随后的“激发”性苯丙胺给药后的注意力表现。
训练大鼠执行一项双杠杆持续注意力任务，该任务涉及视觉信号辨别和无信号呈现。达到标准后，将实验对象分为接受递增剂量苯丙胺或生理盐水组。在递增剂量苯丙胺给药后、对接受苯丙胺预处理的大鼠进行“激发”性苯丙胺给药（1.0毫克/千克）后以及激发给药后3天，评估注意力表现。在本实验结束时，对接受生理盐水预处理的大鼠进行剂量反应研究，以确认激发剂量的适宜性。
接受苯丙胺预处理的动物在递增剂量苯丙胺给药后，非信号试验中的错误出现短暂增加。在激发性苯丙胺给药期间及之后，按压杠杆的潜伏期缩短。在剂量反应实验中，给予1.0毫克/千克苯丙胺并未改变接受苯丙胺预处理动物或接受生理盐水预处理动物的准确性。
先前递增剂量的苯丙胺给药短暂地扰乱了注意力，增加了在无信号呈现的试验中对信号的错误“判断”。目前的数据支持现有文献观点，即递增剂量的苯丙胺给药方案可能有助于模拟导致精神分裂症精神病性症状的注意力缺陷。
