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在新生 Sprague Dawley 大鼠的关键期内长时间暴露于甲基苯丙胺并不会加重自我中心和客体中心学习缺陷,但会增加参照记忆损伤。

Prolonged methamphetamine exposure during a critical period in neonatal Sprague Dawley rats does not exacerbate egocentric and allocentric learning deficits but increases reference memory impairments.

机构信息

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.

出版信息

Int J Dev Neurosci. 2020 May;80(3):163-174. doi: 10.1002/jdn.10014. Epub 2020 Mar 6.

Abstract

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.

摘要

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。

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