{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:25:20Z","timestamp":1792203920056,"version":"4.4.0"},"reference-count":71,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There is a growing concern related to the use of opioid maintenance treatment during pregnancy. Studies in both humans and animals have reported reduced cognitive functioning in offspring prenatally exposed to methadone or buprenorphine; however, little is known about the neurobiological mechanisms underlying these impairments. To reveal possible neurobiological effects of such in utero exposure, we examined brain tissue from methadone\u2010 and buprenorphine\u2010exposed rat offspring previously shown to display impaired learning and memory. We studied \u00b5\u2010opioid receptor (MOR) and N\u2010methyl\u2010D\u2010aspartate receptor (NMDAR) binding in the rat offspring cerebrum during development and in the hippocampus at young adulthood. Moreover, we examined activation of the Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent protein kinase II (CaMKII) and the extracellular signal\u2010regulated kinase (ERK), which are central in the downstream signaling of these receptors. The methadone\u2010 and buprenorphine\u2010exposed rat pups displayed reduced MOR binding up to two weeks after birth, whereas the NMDAR binding was unaffected. Prenatal exposure to methadone or buprenorphine also resulted in decreased activation of CaMKII and\/or ERK during development, while young adult offspring displayed increased hippocampal ERK activation. In conclusion, our findings suggest that prenatal exposure to exogenous opioids, such as methadone or buprenorphine, may disturb the endogenous opioid system during development, with long\u2010term effects on proteins important for cognitive functioning.<\/jats:p>","DOI":"10.1002\/jdn.10043","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T21:49:40Z","timestamp":1591134580000},"page":"443-453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Prenatal exposure to methadone or buprenorphine alters \u00b5\u2010opioid receptor binding and downstream signaling in the rat brain"],"prefix":"10.1002","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2115-053X","authenticated-orcid":false,"given":"Mette","family":"Kongstorp","sequence":"first","affiliation":[{"name":"Department of Forensic Sciences Oslo University Hospital Oslo Norway"},{"name":"Institute of Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2877-0624","authenticated-orcid":false,"given":"Inger Lise","family":"Bogen","sequence":"additional","affiliation":[{"name":"Department of Forensic Sciences Oslo University Hospital Oslo Norway"},{"name":"Institute of Basic Medical Sciences Faculty of Medicine University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Synne","family":"Steinsland","sequence":"additional","affiliation":[{"name":"Department of Forensic Sciences Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Nerem","sequence":"additional","affiliation":[{"name":"Department of Forensic Sciences Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2819-2043","authenticated-orcid":false,"given":"Triske Woshyar","family":"Salih","sequence":"additional","affiliation":[{"name":"Department of Forensic Sciences Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Stiris","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway"},{"name":"Department of Neonatal Intensive Care Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8425-9743","authenticated-orcid":false,"given":"Jannike M\u00f8rch","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Forensic Sciences Oslo University Hospital Oslo Norway"},{"name":"Department of Pharmacy Faculty of Mathematics and Natural Sciences University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318238bba6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2020.104997"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-015-0438-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1479-828X.2012.01424.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(98)00117-5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(94)90100-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S70585"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12929-015-0126-2","article-title":"Beneficial effects of co\u2010treatment with dextromethorphan on prenatally methadone\u2010exposed offspring","volume":"22","author":"Chiang Y. 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