Paternal morphine self-administration produces object recognition memory deficits in female, but not male offspring
Paternal morphine self-administration produces object recognition memory deficits in female, but not male offspring
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DOI：
10.1007/s00213-019-05450-6
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发表时间：
2020-04-01
影响因子：
3.4
通讯作者：
Wimmer, Mathieu E.
中科院分区：
文献类型：
--
作者：
Ellis, Alexandra S.;Toussaint, Andre B.;Wimmer, Mathieu E.
理由：父母在怀孕前后或怀孕前使用药物会对后代产生不良后果。从历史上看，这项研究主要集中在母亲物质使用对后代的影响上，但对父亲血统的影响知之甚少。本研究的重点是怀孕前父亲长期暴露吗啡对男性和女性后代行为结果的影响。目的探讨父亲吗啡自我给药对雄性和雌性后代焦虑样行为、应激反应和记忆的影响。方法采用防御性探针埋置和新奇性下咽范式对吗啡治疗组和对照组的成年、未用药的男性和女性后代的焦虑样行为进行评估。下丘脑-垂体-肾上腺（HPA）轴功能是通过测量血浆皮质酮水平在一个约束应激源后的雄性和雌性后代进行评估。记忆是通过一系列测试来探测的，包括物体定位记忆、新物体识别和情境恐惧条件反射。结果父亲吗啡暴露不改变雄性或雌性后代的焦虑样行为或应激诱导的HPA轴激活。注射吗啡的雄性和雌性后代表现出完整的海马体依赖性记忆：它们在长期恐惧条件反射和物体定位记忆测试中表现正常。相比之下，父亲的吗啡暴露选择性地破坏了雌性后代对新物体的识别，而不是雄性后代。本研究结果表明，父亲服用吗啡会导致目标识别记忆的性别特异性和选择性损伤，而海马功能基本完好无损。
Rationale Parental drug use around or before conception can have adverse consequences for offspring. Historically, this research has focused on the effects of maternal substance use on future generations but less is known about the influence of the paternal lineage. This study focused on the impact of chronic paternal morphine exposure prior to conception on behavioral outcomes in male and female progeny. Objectives This study sought to investigate the impact of paternal morphine self-administration on anxiety-like behavior, the stress response, and memory in male and female offspring. Methods Adult, drug-naive male and female progeny of morphine-treated sires and controls were evaluated for anxiety-like behavior using defensive probe burying and novelty-induced hypophagia paradigms. Hypothalamic-pituitary-adrenal (HPA) axis function was assessed by measuring plasma corticosterone levels following a restraint stressor in male and female progeny. Memory was probed using a battery of tests including object location memory, novel object recognition, and contextual fear conditioning. Results Paternal morphine exposure did not alter anxiety-like behavior or stress-induced HPA axis activation in male or female offspring. Morphine-sired male and female offspring showed intact hippocampus-dependent memory: they performed normally on the long-term fear conditioning and object location memory tests. In contrast, paternal morphine exposure selectively disrupted novel object recognition in female, but not male, progeny. Conclusions Our findings demonstrate that paternal morphine taking produces sex-specific and selective impairments in object recognition memory while leaving hippocampal function largely intact.