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围产期阿片类物质暴露改变青春期大鼠酒精驱动的奖赏行为。

Perigestational Opioid Exposure Alters Alcohol-Driven Reward Behaviors in Adolescent Rats.

作者信息

Searles Christopher T, Harder Hannah J, Vogt Meghan E, Murphy Anne Z

机构信息

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

出版信息

bioRxiv. 2023 Nov 16:2023.11.14.567041. doi: 10.1101/2023.11.14.567041.

Abstract

Every fifteen minutes, a baby is born in the U.S. experiencing neonatal opioid withdrawal syndrome (NOWS). Since 2004, the rate of NOWS has increased 7-fold. Clinical studies have established intrauterine exposure to drugs of abuse as a risk factor for adverse health outcomes in adult life, including the propensity for future illicit drug use. Despite extensive knowledge about common mechanisms of action in the neural circuitry that drives opioid and alcohol reward, there is little data on the risks that those born with NOWS face regarding alcohol use later in life. Here, we investigate the impact of perigestational opioid exposure (POE) on the mesolimbic reward system of male and female Sprague Dawley rats at postnatal and adolescent ages. Our laboratory has developed a clinically relevant model for morphine exposure spanning pre-conception to the first week of life. Using this model, we found that POE increased alcohol consumption in female rats under noncontingent conditions, and inversely, reduced alcohol consumption in both male and female rats during operant conditioning sessions. Operant responding was also reduced for sucrose, suggesting that the impact of POE on reward-seeking behaviors is not limited to drugs of abuse. Expression of μ-opioid receptors was also significantly altered in the nucleus accumbens and medial habenula, regions previously shown to play a significant role in reward/aversion circuitry.

摘要

在美国,每隔15分钟就有一名新生儿出现新生儿阿片类药物戒断综合征(NOWS)。自2004年以来,NOWS的发病率增长了7倍。临床研究已证实,子宫内暴露于滥用药物是成年后不良健康后果的一个风险因素,包括未来使用非法药物的倾向。尽管人们对驱动阿片类药物和酒精奖赏的神经回路中的常见作用机制有广泛了解,但关于患有NOWS的人在成年后饮酒所面临风险的数据却很少。在此,我们研究围产期阿片类药物暴露(POE)对出生后和青春期的雄性和雌性Sprague Dawley大鼠中脑边缘奖赏系统的影响。我们实验室已开发出一种从受孕前到出生后第一周的吗啡暴露临床相关模型。利用该模型,我们发现POE在非偶然条件下增加了雌性大鼠的酒精摄入量,相反,在操作性条件反射实验中,POE降低了雄性和雌性大鼠的酒精摄入量。对蔗糖的操作性反应也减少了,这表明POE对奖赏寻求行为的影响并不局限于滥用药物。伏隔核和内侧缰核中μ-阿片受体的表达也发生了显著变化,这些区域先前已被证明在奖赏/厌恶回路中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3500/10680700/4c74ce677605/nihpp-2023.11.14.567041v1-f0001.jpg

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