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The opioid system in the periaqueductal gray (PAG) is highly vulnerable to drug exposure. However, the impact of adolescent morphine exposure (AME) on the endogenous opioid system in the PAG is currently unknown. This study aims to investigate the long\u2010lasting effects of AME on the endogenous opioid system and its involvement in altering nociceptive behaviors. Adolescent rats were given escalating doses of morphine (2.5\u201325\u00a0mg\/kg, subcutaneous) or an equal volume of saline twice daily for 10 consecutive days (PND 31\u201340). After a 30\u2010day washout period, adult rats underwent formalin tests following microinjection of morphine, naloxone, or saline into the ventrolateral PAG (vlPAG) region. The results indicated that morphine microinjection into the vlPAG of the adolescent morphine\u2010treated group significantly reduced the nociceptive score. However, the analgesic response to morphine in this group was significantly lower compared to the saline\u2010treated group during adolescence. Additionally, the nociceptive score significantly increased following naloxone but not saline microinjection into the vlPAG of the saline\u2010treated group during adolescence, rather than the morphine\u2010treated one. These findings indicate that AME has long\u2010lasting effects on the endogenous opioid system in the vlPAG, which can consequently alter behaviors related to inflammatory pain in adulthood.<\/jats:p>","DOI":"10.1002\/dev.22447","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T02:35:03Z","timestamp":1702262103000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Adolescent morphine exposure changes the endogenous vlPAG opioid response to inflammatory pain in rats"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7597-4171","authenticated-orcid":false,"given":"Kawsar","family":"Alami","sequence":"first","affiliation":[{"name":"Department of Physiology Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmira","family":"Ghasemi","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Semnanian","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8489-0861","authenticated-orcid":false,"given":"Hossein","family":"Azizi","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104615\u20103302\u20103_1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410040511"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901870304"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0301\u20100082(95)00009\u2010K"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(79)90942\u20109"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2020.108025"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.09.008"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2010.11.059"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2016.08.002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13378"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2005.05.009"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.09.016"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103959(77)90130\u20100"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2011.02.357"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2008.06.009"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091\u20103057(93)90558\u2010B"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006\u20108993(02)03661\u20102"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.06.011"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/dev.21790"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-11-770"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12753"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2018.00425"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(99)00033-0"},{"key":"e_1_2_9_25_1","unstructured":"International Association for the Study of Pain (IASP). 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