Carson Dean S, Arnold Simon J, Carson Emily R T, Pascual Conrado, Xie Xinmin Simon
Katana Pharmaceuticals Inc. San Francisco, California, 94103, USA.
Queensland Health, Obstetrics & Gynaecology, Queensland, 4510, Australia.
Compr Psychoneuroendocrinol. 2022 May 18;11:100143. doi: 10.1016/j.cpnec.2022.100143. eCollection 2022 Aug.
Prenatal exposure to drugs of abuse results in neonatal abstinence syndrome (NAS). NAS causes significant morbidity and is associated with costly and lengthy hospitalization. Current pharmacotherapy is suboptimal with no FDA approved treatments. We examined the effect of postnatal oxytocin treatment on survival and neurodevelopmental outcomes in rats prenatally exposed to opioids or benzodiazepines. Sprague-Dawley rat dams were injected with escalating doses of morphine (10-50 mg/kg/day) or diazepam (2-15 mg/kg/day) throughout gestation. In an initial experiment, exposed rat pups received subcutaneous injections of 2 mg/kg oxytocin or saline for the first 10 postnatal days and survival rates were assessed. In a second experiment, exposed rat pups received subcutaneous injections of 0.3, 1, or 2 mg/kg oxytocin or saline for the first 10 postnatal days and survival and body weight were assessed for 30 days. In animals surviving through adolescence, neurodevelopmental outcomes and biological parameters (blood glucose, corticosterone, aldosterone) were also measured. Postnatal oxytocin treatment improved survival in animals prenatally exposed to morphine or diazepam. Preliminary evidence showed that postnatal oxytocin treatment improves long-term learning and memory processes in animals prenatally exposed to morphine or diazepam. These findings highlight the potential of oxytocin as a novel treatment for NAS resulting from prenatal exposure to opioids or benzodiazepines.
产前暴露于滥用药物会导致新生儿戒断综合征（NAS）。NAS会引发严重的发病率，并与昂贵且漫长的住院治疗相关。目前的药物治疗效果欠佳，尚无美国食品药品监督管理局（FDA）批准的治疗方法。我们研究了产后催产素治疗对产前暴露于阿片类药物或苯二氮䓬类药物的大鼠的生存及神经发育结局的影响。在整个妊娠期，对斯普拉格-道利大鼠母鼠注射递增剂量的吗啡（10 - 50毫克/千克/天）或地西泮（2 - 15毫克/千克/天）。在最初的实验中，对暴露的大鼠幼崽在出生后的前10天皮下注射2毫克/千克的催产素或生理盐水，并评估存活率。在第二个实验中，对暴露的大鼠幼崽在出生后的前10天皮下注射0.3、1或2毫克/千克的催产素或生理盐水，并在30天内评估存活率和体重。对于存活至青春期的动物，还测量了神经发育结局和生物学参数（血糖、皮质酮、醛固酮）。产后催产素治疗提高了产前暴露于吗啡或地西泮的动物的存活率。初步证据表明，产后催产素治疗改善了产前暴露于吗啡或地西泮的动物的长期学习和记忆过程。这些发现凸显了催产素作为一种针对产前暴露于阿片类药物或苯二氮䓬类药物所致NAS的新型治疗方法的潜力。
