Effects of Morphine and Maternal Care on Behaviors and Protein Expression of Male Offspring
Effects of Morphine and Maternal Care on Behaviors and Protein Expression of Male Offspring
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DOI：
10.1016/j.neuroscience.2021.04.011
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发表时间：
2021-05-21
期刊：
影响因子：
3.3
通讯作者：
Zarrindast, Mohammad-Reza
中科院分区：
文献类型：
--
作者：
Akbarabadi, Ardeshir;Sadat-Shirazi, Mitra-Sadat;Zarrindast, Mohammad-Reza
基因和环境在发育过程中相互作用，改变基因表达和行为。父母在怀孕前接触吗啡对后代有毁灭性的影响。在本研究中，我们评估的作用，产妇护理的代际效应的母亲吗啡暴露。雌性大鼠接受吗啡或生理盐水10天，并在另一个10天没有药物。此后，它们被允许与未用药的雄性大鼠交配。当幼崽出生时，他们被交叉寄养，以评估母体护理与吗啡对后代影响的贡献。成年雄性后代的焦虑样行为，空间记忆和强迫样行为进行了检查。为了确定所观察到的行为变化的潜在机制，在脑中测量乙酰化组蛋白H3、BDNF、Trk-B、NMDA亚基、p-CREB和5-HT 3R的蛋白水平。我们的研究结果表明，母亲的生育能力是受损的吗啡戒断的母亲。有趣的是，母亲的照顾行为也受到影响，在药物幼稚的母亲，提高后代的吗啡暴露的母亲。此外，吗啡戒断和非药物依赖母亲的后代，当由吗啡戒断母亲抚养时，表现出更多的焦虑，强迫行为和受损的空间记忆。这些改变的行为与上述蛋白质水平的改变有关。这些数据说明了母体吗啡暴露对后代行为的代际影响。此外，妊娠前暴露于吗啡不仅会影响母亲的护理和后代的行为，而且还会对受影响后代的养母的行为和蛋白质表达产生负面影响。(C)2021年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Genes and environment interact during development to alter gene expression and behavior. Parental morphine exposure before conception has devastating effects on the offspring. In the present study, we evaluated the role of maternal care in the intergenerational effect of maternal morphine exposure. Female rats received morphine or saline for ten days and were drugfree for another ten days. Thereafter, they were allowed to mate with drug-naive male rats. When pups were born, they were cross-fostered to assess the contribution of maternal care versus morphine effects on the offspring. Adult male offspring were examined for anxiety-like behavior, spatial memory, and obsessive-compulsive-like behavior. To determine the mechanisms underlying the observed behavioral changes, protein levels of acetylated histone H3, BDNF, Trk-B, NMDA subunits, p-CREB, and 5-HT3R were measured in the brain. Our results indicate that maternal caregiving is impaired in morphine-abstinent mothers. Interestingly, maternal care behaviors were also affected in drug-naive mothers that raised offspring of morphine-exposed mothers. In addition, the offspring of morphine abstinent and non-drug dependent mothers, when raised by morphine abstinent mothers, exhibited more anxiety, obsessive-compulsive behaviors and impaired spatial memory. These altered behaviors were associated with alterations in the levels of the abovementioned proteins. These data illustrate the intergenerational effects of maternal morphine exposure on offspring behaviors. Moreover, exposure to morphine before gestation not only affects maternal care and offspring behavior, but also has negative consequences on behaviors and protein expression in adoptive mothers of affected offspring. (C) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.