Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Division of Neurology (MLC 7044), Cincinnati Children's Research Foundation, Cincinnati, OH, USA.
Int J Dev Neurosci. 2020 May;80(3):163-174. doi: 10.1002/jdn.10014. Epub 2020 Mar 6.
Children exposed to methamphetamine (MA) in utero have cognitive deficits. MA administration in rats for 5-10 days between postnatal days (P)6 and 20 produces cognitive deficits. The purpose of this study was to determine if extending MA administration by 5 days within P6-20 would exacerbate allocentric (Morris water maze) and egocentric (Cincinnati water maze) learning deficits. Sprague Dawley female and male offspring (split-litter design) were administered saline (SAL) or MA (10 mg/kg) four times daily from P6 to 20 to create four groups: (a) SAL from P6 to 20, (b) MA from P6 to 20 (MA6-20), (c) MA from P6 to 15 (MA6-15), or (d) MA from P11 to 20 (MA11-20); the latter groups received saline on days they did not receive MA. Egocentric, allocentric, and conditioned freezing tests began on P60. The MA6-15 and MA6-20 groups showed egocentric deficits, all MA groups had allocentric deficits but no differences in conditioned freezing compared with SAL controls. The MA6-15 and MA6-20 groups had similar deficits in learning and memory that were larger than in the MA11-20 group. Learning in both mazes was sex dependent, but no interactions with MA were found. The data demonstrate that extending the exposure period of MA beyond the sensitive periods (P6-15 and P11-20) did not exacerbate the cognitive deficits.
子宫内暴露于甲基苯丙胺(MA)的儿童存在认知缺陷。在新生后第 6 至 20 天(P)期间,给大鼠连续 5-10 天给予 MA 会导致认知缺陷。本研究的目的是确定在 P6-20 期间将 MA 给药时间延长 5 天是否会加剧非自我中心(莫里斯水迷宫)和自我中心(辛辛那提水迷宫)学习缺陷。使用 Sprague Dawley 雌性和雄性后代(分裂 litter 设计),从 P6 至 20 每天给予盐水(SAL)或 MA(10mg/kg)四次,创建四个组:(a)P6 至 20 期间给予 SAL,(b)P6 至 20 期间给予 MA(MA6-20),(c)P6 至 15 期间给予 MA(MA6-15),或(d)P11 至 20 期间给予 MA(MA11-20);后两组在未接受 MA 的日子接受 SAL。自我中心、非自我中心和条件性冻结测试于 P60 开始。MA6-15 和 MA6-20 组表现出自我中心缺陷,所有 MA 组均存在非自我中心缺陷,但与 SAL 对照组相比,条件性冻结无差异。MA6-15 和 MA6-20 组在学习和记忆方面的缺陷相似,且比 MA11-20 组更大。两种迷宫中的学习均依赖于性别,但未发现与 MA 的相互作用。数据表明,将 MA 的暴露期延长至敏感期(P6-15 和 P11-20)之外不会加剧认知缺陷。