{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T01:21:59Z","timestamp":1783041719605,"version":"3.54.6"},"reference-count":101,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Center, Cairo, Egypt","award":["#12060142"],"award-info":[{"award-number":["#12060142"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>We have examined the effects of four different polyphenols in attenuating heroin addiction using a conditioned place preference (CPP) paradigm. Adult male Sprague Dawley rats received heroin (alternating with saline) in escalating doses starting from 10 mg\/kg, i.p. up to 80 mg\/kg\/d for 14 consecutive days. The rats were treated with distilled water (1 mL), quercetin (50 mg\/kg\/d), \u03b2-catechin (100 mg\/kg\/d), resveratrol (30 mg\/kg\/d), or magnolol (50 mg\/kg\/d) through oral gavage for 7 consecutive days, 30 min before heroin administration, starting on day 8. Heroin withdrawal manifestations were assessed 24 h post last heroin administration following the administration of naloxone (1 mg\/kg i.p). Heroin CPP reinstatement was tested following a single dose of heroin (10 mg\/kg i.p.) administration. Striatal interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-\u03b1) were quantified (ELISA) after naloxone-precipitated heroin withdrawal. Compared to the vehicle, the heroin-administered rats spent significantly more time in the heroin-paired chamber (p &lt; 0.0001). Concomitant administration of resveratrol and quercetin prevented the acquisition of heroin CPP, while resveratrol, quercetin, and magnolol blocked heroin-triggered reinstatement. Magnolol, quercetin, and \u03b2-catechin blocked naloxone-precipitated heroin withdrawal and increased striatal IL-6 concentration (p &lt; 0.01). Resveratrol administration was associated with significantly higher withdrawal scores compared to those of the control animals (p &lt; 0.0001). The results of this study show that different polyphenols target specific behavioral domains of heroin addiction in a CPP model and modulate the increase in striatal inflammatory cytokines TNF-\u03b1 and IL-6 observed during naloxone-precipitated heroin withdrawal. Further research is needed to study the clinical utility of polyphenols and to investigate the intriguing finding that resveratrol enhances, rather than attenuates naloxone-precipitated heroin withdrawal.<\/jats:p>","DOI":"10.3390\/toxics11040379","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T04:45:32Z","timestamp":1681706732000},"page":"379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Natural Polyphenols\u2014Resveratrol, Quercetin, Magnolol, and \u03b2-Catechin\u2014Block Certain Aspects of Heroin Addiction and Modulate Striatal IL-6 and TNF-\u03b1"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3927-7464","authenticated-orcid":false,"given":"Shaimaa","family":"ElShebiney","sequence":"first","affiliation":[{"name":"Department of Narcotics, Ergogenics, and Poisons, National Research Centre, Dokki, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Elgohary","sequence":"additional","affiliation":[{"name":"Department of Narcotics, Ergogenics, and Poisons, National Research Centre, Dokki, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"El-Shamarka","sequence":"additional","affiliation":[{"name":"Department of Narcotics, Ergogenics, and Poisons, National Research Centre, Dokki, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha","family":"Mowaad","sequence":"additional","affiliation":[{"name":"Department of Narcotics, Ergogenics, and Poisons, National Research Centre, Dokki, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama A.","family":"Abulseoud","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic, Phoenix, AZ 85001, USA"},{"name":"Department of Neuroscience, Graduate School of Biomedical Sciences, Mayo Clinic College of Medicine, Phoenix, AZ 85001, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1016\/S0140-6736(13)61530-5","article-title":"Global burden of disease attributable to illicit drug use and dependence: Findings from the Global Burden of Disease Study 2010","volume":"382","author":"Degenhardt","year":"2013","journal-title":"Lancet"},{"key":"ref_2","unstructured":"Lipari, R.N., and Hughes, A. 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