Differential Effects of Prenatal Buprenorphine and Methadone on Postnatal Growth and Gene Expression in the Nucleus Accumbens

IF 1.8 4区 心理学 Q3 DEVELOPMENTAL BIOLOGY Developmental psychobiology Pub Date : 2024-12-08 DOI:10.1002/dev.70015
Kelsea R. Gildawie, Kerri E. Budge, Fair M. Vassoler, Elizabeth Yen, Elizabeth M. Byrnes
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Abstract

Methadone and buprenorphine are commonly prescribed during pregnancy to maintain recovery and prevent symptoms of withdrawal in women with opioid use disorder. Infants prenatally exposed to medications for opioid use disorder (MOUD), however, commonly show signs of neonatal opioid withdrawal syndrome (NOWS), which can include feeding-related issues like hyperphagia. To investigate the effects of prenatal MOUD exposure on feeding behavior, female Sprague-Dawley rats were implanted with osmotic minipumps filled with methadone, buprenorphine, or saline and subsequently mated. On postnatal day (PND) 1, buprenorphine- and methadone-exposed offspring weighed less than saline-exposed subjects. Throughout early postnatal development (PND2, 7, and 12), this reduction in weight persisted in buprenorphine, but not methadone, offspring. RNAscope in situ hybridization was then used to measure expression of genes in the nucleus accumbens (NAc) previously associated with hyperphagia in NOWS infants, including proopiomelanocortin (Pomc), neuropeptide Y2 receptors (Npy2r), and dopamine type 2 receptors (Drd2). Distinct developmental expression patterns were noted across the postnatal period, with few effects of MOUD; however, significantly lower Pomc expression was observed in methadone-exposed but not buprenorphine-exposed offspring. These findings demonstrate differential effects of methadone and buprenorphine on offspring development and gene expression, highlighting differences in offspring outcomes associated with these two MOUDs.

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产前丁丙诺啡和美沙酮对出生后伏隔核生长和基因表达的差异影响。
美沙酮和丁丙诺啡通常在怀孕期间开处方,以维持阿片类药物使用障碍妇女的恢复和预防戒断症状。然而,产前暴露于阿片类药物使用障碍(mod)药物的婴儿通常表现出新生儿阿片类药物戒断综合征(NOWS)的迹象,其中可能包括与喂养相关的问题,如嗜食。为了研究产前暴露于mod对摄食行为的影响,雌性Sprague-Dawley大鼠被植入充满美沙酮、丁丙诺啡或生理盐水的渗透微型泵,随后进行交配。产后1日,丁丙诺啡和美沙酮暴露的后代体重低于盐暴露者。在出生后早期发育过程中(PND2、7和12),丁丙诺啡的后代体重持续下降,而美沙酮的后代则没有。然后使用RNAscope原位杂交技术测量先前与NOWS婴儿贪食相关的伏隔核(NAc)中基因的表达,包括proopiomelanocortin (Pomc),神经肽Y2受体(Npy2r)和多巴胺2型受体(Drd2)。不同的发育表达模式在出生后被注意到,mod的影响很小;然而,暴露于美沙酮而非丁丙诺啡的后代的Pomc表达显著降低。这些发现表明美沙酮和丁丙诺啡对后代发育和基因表达的不同影响,突出了与这两种mod相关的后代结局的差异。
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来源期刊
Developmental psychobiology
Developmental psychobiology 生物-发育生物学
CiteScore
4.20
自引率
18.20%
发文量
125
审稿时长
6-12 weeks
期刊介绍: Developmental Psychobiology is a peer-reviewed journal that publishes original research papers from the disciplines of psychology, biology, neuroscience, and medicine that contribute to an understanding of behavior development. Research that focuses on development in the embryo/fetus, neonate, juvenile, or adult animal and multidisciplinary research that relates behavioral development to anatomy, physiology, biochemistry, genetics, or evolution is appropriate. The journal represents a broad phylogenetic perspective on behavior development by publishing studies of invertebrates, fish, birds, humans, and other animals. The journal publishes experimental and descriptive studies whether carried out in the laboratory or field. The journal also publishes review articles and theoretical papers that make important conceptual contributions. Special dedicated issues of Developmental Psychobiology , consisting of invited papers on a topic of general interest, may be arranged with the Editor-in-Chief. Developmental Psychobiology also publishes Letters to the Editor, which discuss issues of general interest or material published in the journal. Letters discussing published material may correct errors, provide clarification, or offer a different point of view. Authors should consult the editors on the preparation of these contributions.
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