Dietary polyphenols drive dose-dependent behavioral and molecular alterations to repeated morphine.
Dietary polyphenols drive dose-dependent behavioral and molecular alterations to repeated morphine.
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DOI：
10.1038/s41598-023-39334-9
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发表时间：
2023-07-27
影响因子：
4.6
通讯作者：
Kiraly, Drew D.
中科院分区：
文献类型：
--
作者：
Osman, Aya;Hofford, Rebecca S.;Meckel, Katherine R.;Dave, Yesha A.;Zeldin, Sharon M.;Shipman, Ava L.;Lucerne, Kelsey E.;Trageser, Kyle J.;Oguchi, Tatsunori;Kiraly, Drew D.
阿片类药物使用障碍 (OUD) 与巨大的发病率和死亡率相关。尽管存在这种负担，但目前的 OUD 药物疗法对许多患者来说仍然无效或无法耐受。因此，旨在提高 OUD 抵抗力的干预措施具有巨大的临床意义。使用生物活性膳食多酚制剂 (BDPP) 治疗可促进多种神经精神疾病模型的恢复力和适应性神经可塑性。在这里，我们评估了 BDPP 治疗对雄性小鼠重复吗啡治疗的行为和分子反应的影响。 BDPP 预处理改变了运动敏化和条件性位置偏好的反应。最值得注意的是，多酚治疗持续降低了低剂量（5 mg/kg）吗啡的偏好形成，但增强了高剂量（15 mg/kg）吗啡的偏好形成。与此同时，我们对伏隔核进行了转录组分析，再次显示了剂量×多酚的相互作用。我们还分析了微生物组的组成和功能，因为多酚由微生物组代谢并可以充当益生元。该图显示多酚处理显着改变了微生物组的组成和功能。最后，我们研究了 SIRT1 脱乙酰酶的参与以及多酚代谢物在行为反应中的作用。这些结果表明多酚对吗啡的行为和生理反应具有强大的剂量依赖性影响，并为未来的转化工作奠定了基础。
Opioid Use Disorder (OUD) is associated with tremendous morbidity and mortality. Despite this burden, current pharmacotherapies for OUD are ineffective or intolerable for many patients. As such, interventions aimed at promoting resilience against OUD are of immense clinical interest. Treatment with a Bioactive Dietary Polyphenol Preparation (BDPP) promotes resilience and adaptive neuroplasticity in multiple models of neuropsychiatric disease. Here, we assessed effects of BDPP treatment on behavioral and molecular responses to repeated morphine treatment in male mice. BDPP pre-treatment alters responses for both locomotor sensitization and conditioned place preference. Most notably, polyphenol treatment consistently reduced formation of preference at low dose (5 mg/kg) morphine but enhanced it at high dose (15 mg/kg). In parallel, we performed transcriptomic profiling of the nucleus accumbens, which again showed a dose × polyphenol interaction. We also profiled microbiome composition and function, as polyphenols are metabolized by the microbiome and can act as prebiotics. The profile revealed polyphenol treatment markedly altered microbiome composition and function. Finally, we investigated involvement of the SIRT1 deacetylase, and the role of polyphenol metabolites in behavioral responses. These results demonstrate polyphenols have robust dose-dependent effects on behavioral and physiological responses to morphine and lay the foundation for future translational work.
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