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This study aimed to explore the influence of parental morphine exposure 10 days prior to pregnancy on drug\u2010induced locomotor sensitization. Adult male and female Wistar rats were categorized into morphine\u2010exposed and control groups. Ten days after their last treatment, they were mated, and their male offspring underwent morphine, methamphetamine, cocaine, and nicotine\u2010induced locomotor sensitization tests. The results indicated increased locomotor activity in both groups after drug exposure, although the changes were attenuated in morphine and cocaine sensitization among the offspring of morphine\u2010exposed parents (MEPs). Western blotting analysis revealed altered levels of D2 dopamine receptors (D2DRs) in the prefrontal cortex and nucleus accumbens of the offspring from MEPs. Remarkably, despite not having direct in utero drug exposure, these offspring exhibited molecular alterations affecting morphine and cocaine\u2010induced sensitization. The diminished sensitization to morphine and cocaine suggested the development of a tolerance phenotype in these offspring. The changes in D2DR levels in the brain might play a role in these adaptations.<\/jats:p>","DOI":"10.1002\/dev.22514","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T04:28:26Z","timestamp":1719289706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Parental Exposure to Morphine Before Conception Decreases Morphine and Cocaine\u2010Induced Locomotor Sensitization in Male Offspring"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4327-8814","authenticated-orcid":false,"given":"Amirhossein","family":"Heidari","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Tehran Medical Sciences Islamic Azad University  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3264-5631","authenticated-orcid":false,"given":"Arman","family":"Hajikarim\u2010Hamedani","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tehran Medical Sciences Islamic Azad University  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saereh","family":"Hosseindoost","sequence":"additional","affiliation":[{"name":"Pain Research Center, Neuroscience Institute, Imam Khomeini Hospital Complex Tehran University of Medical Sciences  Tehran Iran"},{"name":"Brain and Spinal Cord Injury Research Center, Neuroscience Institute Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7309-4066","authenticated-orcid":false,"given":"Yekta","family":"Ghane","sequence":"additional","affiliation":[{"name":"School of Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1905-2500","authenticated-orcid":false,"given":"Mitra","family":"Sadat\u2010Shirazi","sequence":"additional","affiliation":[{"name":"Development, Molecular &amp; Chemical Biology Tufts University  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0688-5378","authenticated-orcid":false,"given":"Mohammad\u2010Reza","family":"Zarrindast","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,6,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2017.11.024"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2017.1398296"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052618"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3810\/pgm.2009.11.2087"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.01.022"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.63.12.1386"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047527"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010005\u20100122\u20104"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2010.11.059"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1037\/\/1064\u20101297.9.3.307"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2022.07.003"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(94)90206\u20102"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092224"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2217\/17455057.4.1.51"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a039628"},{"volume-title":"The Prefrontal Cortex: Anatomy, Physiology, and Neuropsychology of the Frontal Lobe","year":"1997","author":"Fuster J. 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