Williams Michael T, Vorhees Charles V, Boon Francis, Saber Andrea J, Cain Donald P
Pharmacology Research Center, Children's Hospital Research Foundation and University of Cincinnati, 3333 Burnet Ave, Cincinnati, OH 45229-3039, USA.
Brain Res. 2002 Dec 27;958(2):312-21. doi: 10.1016/s0006-8993(02)03620-x.
Spatial learning and memory deficits in a water maze have been observed in adult animals exposed to a regimen of 4 daily doses of d-methamphetamine (MA) at 2 h intervals from postnatal day 11 to 20. An interpretational issue for these long-term effects of MA is whether they are truly spatial deficits or are secondary to alterations in sensorimotor systems. In this experiment, we evaluated the effects of a pretraining procedure shown to minimize the influence of drug-induced sensorimotor deficits. Animals within a litter were treated with MA or saline. Animals were either pretrained for nonspatial task requirements in the water maze (i.e., swimming and platform climbing) or were nai;ve to the task. Animals that received the pretraining did better than the nai;ve animals. The nai;ve MA animals performed worse than the nai;ve control animals as previously observed. By contrast, no difference in search time was noted between pretrained MA- and SAL-treated animals during the acquisition phase of testing. When the platform was relocated in a novel position, spatial learning was impaired for MA animals, regardless of pretraining. No increase in the number of platform nonrecognition events (swimovers, deflections, or jump-offs) occurred among pretrained or nai;ve groups compared to controls. These data suggest that sensorimotor deficits do not account for the spatial learning and memory deficits in animals exposed neonatally to MA.
在出生后第11天至20天,成年动物每天接受4次剂量的d-甲基苯丙胺(MA)注射,每次间隔2小时,在水迷宫实验中观察到其空间学习和记忆缺陷。MA这些长期影响的一个解释问题是,它们是真正的空间缺陷还是继发于感觉运动系统的改变。在本实验中,我们评估了一种预训练程序的效果,该程序已被证明可将药物诱导的感觉运动缺陷的影响降至最低。一窝动物中,部分用MA或生理盐水处理。动物要么在水迷宫中接受非空间任务要求的预训练(即游泳和爬上平台),要么对该任务一无所知。接受预训练的动物比未接受训练的动物表现更好。如先前观察到的,未接受训练的MA处理动物比未接受训练的对照动物表现更差。相比之下,在测试的习得阶段,接受预训练的MA处理动物和生理盐水处理动物之间的搜索时间没有差异。当平台重新放置在新位置时,无论是否接受预训练,MA处理动物的空间学习都受到损害。与对照组相比,在接受预训练或未接受训练的组中,平台未识别事件(游过、偏转或跳下)的数量没有增加。这些数据表明,感觉运动缺陷不能解释新生期暴露于MA的动物的空间学习和记忆缺陷。