Dietary polyphenols drive dose-dependent behavioral and molecular alterations to repeated morphine
Abstract 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. Treatm...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-39334-9 |
| _version_ | 1797769607879065600 |
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| author | Aya Osman Rebecca S. Hofford Katherine R. Meckel Yesha A. Dave Sharon M. Zeldin Ava L. Shipman Kelsey E. Lucerne Kyle J. Trageser Tatsunori Oguchi Drew D. Kiraly |
| author_facet | Aya Osman Rebecca S. Hofford Katherine R. Meckel Yesha A. Dave Sharon M. Zeldin Ava L. Shipman Kelsey E. Lucerne Kyle J. Trageser Tatsunori Oguchi Drew D. Kiraly |
| author_sort | Aya Osman |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T21:10:27Z |
| format | Article |
| id | doaj.art-e71a359cf4a54496baafc4762ebbdb74 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T21:10:27Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e71a359cf4a54496baafc4762ebbdb742023-07-30T11:13:32ZengNature PortfolioScientific Reports2045-23222023-07-0113111310.1038/s41598-023-39334-9Dietary polyphenols drive dose-dependent behavioral and molecular alterations to repeated morphineAya Osman0Rebecca S. Hofford1Katherine R. Meckel2Yesha A. Dave3Sharon M. Zeldin4Ava L. Shipman5Kelsey E. Lucerne6Kyle J. Trageser7Tatsunori Oguchi8Drew D. Kiraly9Department of Psychiatry, Icahn School of Medicine at Mount SinaiDepartment of Psychiatry, Icahn School of Medicine at Mount SinaiFriedman Brain Institute, Icahn School of Medicine at Mount SinaiNash Family Department of Neuroscience, Icahn School of Medicine at Mount SinaiDepartment of Psychiatry, Icahn School of Medicine at Mount SinaiDepartment of Psychiatry, Icahn School of Medicine at Mount SinaiFriedman Brain Institute, Icahn School of Medicine at Mount SinaiDepartment of Neurology, Icahn School of Medicine at Mount SinaiDepartment of Neurology, Icahn School of Medicine at Mount SinaiDepartment of Psychiatry, Icahn School of Medicine at Mount SinaiAbstract 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.https://doi.org/10.1038/s41598-023-39334-9 |
| spellingShingle | Aya Osman Rebecca S. Hofford Katherine R. Meckel Yesha A. Dave Sharon M. Zeldin Ava L. Shipman Kelsey E. Lucerne Kyle J. Trageser Tatsunori Oguchi Drew D. Kiraly Dietary polyphenols drive dose-dependent behavioral and molecular alterations to repeated morphine Scientific Reports |
| title | Dietary polyphenols drive dose-dependent behavioral and molecular alterations to repeated morphine |
| title_full | Dietary polyphenols drive dose-dependent behavioral and molecular alterations to repeated morphine |
| title_fullStr | Dietary polyphenols drive dose-dependent behavioral and molecular alterations to repeated morphine |
| title_full_unstemmed | Dietary polyphenols drive dose-dependent behavioral and molecular alterations to repeated morphine |
| title_short | Dietary polyphenols drive dose-dependent behavioral and molecular alterations to repeated morphine |
| title_sort | dietary polyphenols drive dose dependent behavioral and molecular alterations to repeated morphine |
| url | https://doi.org/10.1038/s41598-023-39334-9 |
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