{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T15:43:41Z","timestamp":1765295021412,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,17]],"date-time":"2018-11-17T00:00:00Z","timestamp":1542412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["9459"],"award-info":[{"award-number":["9459"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kj\u00e4ll and M\u00e4rta Beijer foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/501100003792","name":"Hj\u00e4rnfonden","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Evidence to date suggests that opioids such as methadone may be associated with cognitive impairment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are suggested to be neuroprotective and procognitive in the brain and may therefore counteract these effects. This study aims to explore the protective and restorative effects of GH and IGF-1 in methadone-treated cell cultures. Primary cortical cell cultures were harvested from rat fetuses and grown for seven days in vitro. To examine the protective effects, methadone was co-treated with or without GH or IGF-1 for three consecutive days. To examine the restorative effects, methadone was added for the first 24 h, washed, and later treated with GH or IGF-1 for 48 h. At the end of each experiment, mitochondrial function and membrane integrity were evaluated. The results revealed that GH had protective effects in the membrane integrity assay and that both GH and IGF-1 effectively recovered mitochondrial function and membrane integrity in cells pretreated with methadone. The overall conclusion of the present study is that GH, but not IGF-1, protects primary cortical cells against methadone-induced toxicity, and that both GH and IGF-1 have a restorative effect on cells pretreated with methadone.<\/jats:p>","DOI":"10.3390\/ijms19113627","type":"journal-article","created":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T11:23:27Z","timestamp":1542799407000},"page":"3627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In Vitro"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9683-6034","authenticated-orcid":false,"given":"Erik","family":"Nylander","sequence":"first","affiliation":[{"name":"The Beijer Laboratory, Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, SE-751 24, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Zelleroth","sequence":"additional","affiliation":[{"name":"The Beijer Laboratory, Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, SE-751 24, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Nyberg","sequence":"additional","affiliation":[{"name":"The Beijer Laboratory, Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, SE-751 24, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9780-4168","authenticated-orcid":false,"given":"Alfhild","family":"Gr\u00f6nbladh","sequence":"additional","affiliation":[{"name":"The Beijer Laboratory, Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, SE-751 24, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9835-870X","authenticated-orcid":false,"given":"Mathias","family":"Hallberg","sequence":"additional","affiliation":[{"name":"The Beijer Laboratory, Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, SE-751 24, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1006\/frne.2000.0200","article-title":"Growth hormone in the brain: Characteristics of specific brain targets for the hormone and their functional significance","volume":"21","author":"Nyberg","year":"2000","journal-title":"Front. 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