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吗啡依赖的怀孕大鼠的母性行为紊乱及其后代的快感缺失。

Disrupted maternal behavior in morphine-dependent pregnant rats and anhedonia in their offspring.

作者信息

Searles Christopher T, Vogt Meghan E, Adedokun Iyanuoluwa, Murphy Anne Z

机构信息

Neuroscience Institute, Georgia State University, 100 Piedmont Ave., Atlanta, GA, 30303, USA.

Neuroscience Institute, Georgia State University, 100 Piedmont Ave., Atlanta, GA, 30303, USA.

出版信息

Neuropharmacology. 2025 Jun 1;270:110372. doi: 10.1016/j.neuropharm.2025.110372. Epub 2025 Feb 17.

Abstract

It is currently estimated that every 15 minutes an infant is born with opioid use disorder and undergoes intense early life trauma due to opioid withdrawal. Clinical research on the long-term consequences of gestational opioid exposure reports increased rates of social, conduct, and emotional disorders in these children. Here, we investigate the impact of perinatal opioid exposure (POE) on behaviors associated with anhedonia and stress in male and female Sprague Dawley rats. Young adult female rats were administered morphine via programmable, subcutaneous micro-infusion pumps before, during, and through one week post gestation. For the first two postnatal weeks, maternal behavior was examined for fragmentation and unpredictability. Unpredictable behavioral patterns were quantitatively characterized as entropy scores. Offspring were assessed for sucrose preference, social behavior, and stress responsivity. Overall, dams that received morphine across gestation displayed significantly less pup-directed behavior with increased fragmentation for nursing and higher entropy scores. In adolescence, male and female rat offspring exposed to morphine displayed reduced sucrose preference and, as adults, spent significantly less time interacting with familiar conspecifics. Changes in social behaviors were linked to increased activity in nondopaminergic cells of mesolimbic reward brain regions. Although no treatment effects were observed in forced swim test performance, corticosterone levels were significantly increased in POE adult males. Together, these results suggest that perinatal morphine exposure promotes anhedonic behavior, possibly due to fragmented and unpredictable maternal behavior in opioid-dependent dams.

摘要

目前估计,每15分钟就有一名患有阿片类药物使用障碍的婴儿出生,并且由于阿片类药物戒断而在生命早期遭受严重创伤。关于孕期阿片类药物暴露的长期后果的临床研究报告称,这些儿童出现社交、行为和情绪障碍的比率有所增加。在此,我们研究围产期阿片类药物暴露(POE)对雄性和雌性斯普拉格-道利大鼠与快感缺失和应激相关行为的影响。在妊娠前、妊娠期间以及妊娠后一周,通过可编程皮下微量输注泵对成年雌性大鼠给予吗啡。在出生后的前两周,检查母性行为的碎片化和不可预测性。将不可预测的行为模式定量表征为熵得分。对后代进行蔗糖偏好、社交行为和应激反应性评估。总体而言,在整个妊娠期接受吗啡的母鼠表现出明显更少的亲代抚育行为,护理行为的碎片化增加,熵得分更高。在青春期,暴露于吗啡的雄性和雌性大鼠后代表现出蔗糖偏好降低,并且成年后与熟悉的同种个体互动的时间明显减少。社交行为的变化与中脑边缘奖赏脑区非多巴胺能细胞的活动增加有关。尽管在强迫游泳试验表现中未观察到治疗效果,但POE成年雄性大鼠的皮质酮水平显著升高。总之,这些结果表明围产期吗啡暴露会促进快感缺失行为,这可能是由于阿片类药物依赖的母鼠的碎片化和不可预测的母性行为所致。

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