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母亲在妊娠和哺乳期暴露于卡他碱对其子代小鼠神经精神药理学作用的影响。

The neuropsychopharmacological effects of Catha edulis in mice offspring born to mothers exposed during pregnancy and lactation.

机构信息

Department of Pharmacology, School of Pharmacy, Addis Ababa University, Addis Ababa, Ethiopia.

出版信息

Phytother Res. 2010 Feb;24(2):268-76. doi: 10.1002/ptr.2925.

DOI:10.1002/ptr.2925
PMID:19585482
Abstract

Chewing fresh leaves of the khat plant (Catha edulis Forsk) is a deep rooted and widespread habit in East Africa and the Middle East. Although a body of knowledge exists about the adverse effects of khat during pregnancy, data are sparse with regard to the consequences of long-term exposure during pregnancy and lactation. The present work, therefore, was initiated to evaluate the neuropsychopharmacological effects of Catha edulis exposure during pregnancy and lactation in mice at postnatal day 28. To this effect, a lyophilized extract of khat (100 mg/kg, K100 and 200 mg/kg, K200), amphetamine (1 mg/kg, positive control, AMP), and a similar volume of 2% v/v Tween-80 in distilled water (negative control, CONT) were administered daily to pregnant mice from gestational day 6 until weaning. Neuropsychopharmacological measurements were done by making use of a battery of neurobehavioural and cognitive tests. Moreover, toxicity to liver and kidney was also evaluated by determining biochemical markers for possible tissue damage. K200 produced significant motor in-coordination and emotional instability; as revealed by impairment in both cliff avoidance (p < 0.01) and forelimb grip strength (p < 0.001), as well as by an increase in stereotyped behaviour such as grooming (p < 0.05), and in the percent of time spent in open arms (p < 0.05). On the other hand, K100 had an effect only on grip strength where a decrement was noted (p < 0.01). A different pattern emerged with AMP whilst it increased duration of sniffing (p < 0.05), neither grip strength nor the time spent in the open arm was affected compared with CONT. Increased latency to reach the goal box and the number of wrong decisions (p < 0.05) in both the learning and the recall tests was observed with K200 and AMP. By contrast, both doses of khat and AMP equally affected performance in the Y-maze (p < 0.05). Alterations in the biochemical indices of liver and kidney function were also noted with AMP and K200. These findings indicate that khat exposure produces dose-related central and peripheral effects during pregnancy and lactation which might pose a serious impediment to the physical and mental development of the offspring.

摘要

咀嚼阿拉伯茶(Catha edulis Forsk)的新鲜叶子在东非和中东是一种根深蒂固且广泛存在的习惯。尽管已经有大量关于怀孕时阿拉伯茶的不良影响的知识,但关于怀孕期间和哺乳期长期暴露的后果的数据却很少。因此,本研究旨在评估在产后第 28 天的小鼠中,阿拉伯茶在怀孕期间和哺乳期暴露的神经精神药理学影响。为此,将阿拉伯茶的冻干提取物(100mg/kg,K100 和 200mg/kg,K200)、安非他命(1mg/kg,阳性对照,AMP)和 2%v/v 吐温-80 在蒸馏水中的类似体积(阴性对照,CONT)每天给予怀孕的老鼠,从妊娠第 6 天到断奶。通过使用一系列神经行为和认知测试来进行神经精神药理学测量。此外,还通过测定可能的组织损伤的生化标志物来评估对肝和肾的毒性。K200 导致显著的运动不协调和情绪不稳定;如在悬崖回避(p < 0.01)和前肢握力(p < 0.001)方面的损伤、刻板行为的增加(如梳理(p < 0.05)),以及在开放臂中度过的时间百分比(p < 0.05)中揭示。另一方面,K100 仅对握力有影响,握力下降(p < 0.01)。AMP 则呈现出不同的模式,它增加了嗅探的持续时间(p < 0.05),与 CONT 相比,握力和在开放臂中度过的时间都没有受到影响。K200 和 AMP 都观察到到达目标箱的潜伏期和错误决策的数量增加(p < 0.05),在学习和回忆测试中。相比之下,阿拉伯茶的两种剂量和 AMP 对 Y 型迷宫的表现都有相同的影响(p < 0.05)。AMP 和 K200 还引起了肝功能和肾功能的生化指标的改变。这些发现表明,阿拉伯茶暴露在怀孕期间和哺乳期产生剂量相关的中枢和外周影响,这可能对后代的身体和心理健康发育造成严重阻碍。

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