{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:08:47Z","timestamp":1788959327218,"version":"build-2803163510"},"reference-count":79,"publisher":"Society for Neuroscience","issue":"5","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"HHS | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["K99 DA049908"],"award-info":[{"award-number":["K99 DA049908"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"HHS | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R21 DA049253"],"award-info":[{"award-number":["R21 DA049253"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["eNeuro"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Children exposed prenatally to opioids are at an increased risk for behavioral problems and executive function deficits. The prefrontal cortex (PFC) and amygdala (AMG) regulate executive function and social behavior and are sensitive to opioids prenatally. Opioids can bind to toll-like receptor 4 (TLR4) to activate microglia, which may be developmentally important for synaptic pruning. Therefore, we tested the effects of perinatal morphine exposure on executive function and social behavior in male and female mouse offspring, along with microglial-related and synaptic-related outcomes. Dams were injected once daily subcutaneously with saline (<jats:italic>n<\/jats:italic>\u2009=\u20098) or morphine (MO; 10\u2009mg\/kg;<jats:italic>n<\/jats:italic>\u2009=\u200912) throughout pregestation, gestation, and lactation until offspring were weaned on postnatal day 21 (P21). Male MO offspring had impairments in attention and accuracy in the five-choice serial reaction time task, while female MO offspring were less affected. Targeted gene expression analysis at P21 in the PFC identified alterations in microglial-related and TLR4-related genes, while immunohistochemical analysis in adult brains indicated decreased microglial Iba1 and phagocytic CD68 proteins in the PFC and AMG in males, but females had an increase. Further, both male and female MO offspring had increased social preference. Overall, these data demonstrate male vulnerability to executive function deficits in response to perinatal opioid exposure and evidence for disruptions in neuron\u2013microglial signaling.<\/jats:p>","DOI":"10.1523\/eneuro.0238-22.2022","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T17:50:46Z","timestamp":1665424246000},"page":"ENEURO.0238-22.2022","source":"Crossref","is-referenced-by-count":32,"title":["Perinatal Morphine Exposure Leads to Sex-Dependent Executive Function Deficits and Microglial Changes in Mice"],"prefix":"10.1523","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2745-1461","authenticated-orcid":false,"given":"Brittany L.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tess A.","family":"Guzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander H.","family":"Brendle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin J.","family":"Laaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Ford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam R.","family":"Hiltz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth D. R.","family":"Setchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa M.","family":"Reyes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-021-05888-7"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.6405"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.3","doi-asserted-by":"publisher","DOI":"10.1348\/026151008X314919"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.4","doi-asserted-by":"crossref","unstructured":"Caldwell HK , Albers HE (2016) Oxytocin, vasopressin, and the motivational forces that drive social behaviors. In: Behavioral neuroscience of motivation ( Simpson EH , Balsam PD , eds), pp 51\u2013103. Cham, Switzerland: Springer.","DOI":"10.1007\/7854_2015_390"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.5","doi-asserted-by":"publisher","DOI":"10.1542\/hpeds.2016-0218"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.6","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.08.022"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45971-w"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.9","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.10","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-007-0891-z"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2016.02.006"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2018.11.006"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(97)00281-5"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.14","doi-asserted-by":"publisher","DOI":"10.5115\/acb.2012.45.2.121"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.15","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0393-20.2020"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.16","doi-asserted-by":"publisher","DOI":"10.1089\/pop.2018.0016"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.17","doi-asserted-by":"publisher","DOI":"10.1177\/1178221818765773"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.18","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4603(94)00044-Y"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.19","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.24991"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(96)00274-2"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107899"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2009.08.004"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2019.11.007"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06889.x"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06118-z"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.26","first-page":"118","article-title":"Differential effects of homotypic vs. heterotypic chronic stress regimens on microglial activation in the prefrontal cortex","volume":"193","year":"2013","journal-title":"Physiol Behav"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.27","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2321"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.29","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/20.7.541"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.30","doi-asserted-by":"publisher","DOI":"10.1177\/1073858414536468"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.31","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1268-12.2013"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2017.11.010"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.33","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2020.6364"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.34","doi-asserted-by":"publisher","DOI":"10.1016\/S0892-0362(03)00030-8"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2012.06.023"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.36","doi-asserted-by":"crossref","unstructured":"Mancher M , Leshner AI , eds (2019) Medications for opioid use disorder save lives. Washington, DC: National Academies.","DOI":"10.17226\/25310"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.37","first-page":"2445","article-title":"Autoradiographic differentiation of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain.","volume":"7","year":"1987","journal-title":"J Neurosci"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2014.12.007"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.39","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.61"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.40","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201601172R"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.41","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2020.582147"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.07.026"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.43","first-page":"1","volume-title":"Developmental psychopathology","volume":"Vol 3","year":"2016"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.44","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02368-x"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.45","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2015.95"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158054"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.47","doi-asserted-by":"publisher","DOI":"10.1080\/09297049.2015.1092509"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.48","doi-asserted-by":"publisher","DOI":"10.1016\/0145-2134(96)00014-2"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.49","doi-asserted-by":"publisher","DOI":"10.1126\/science.1202529"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.50","unstructured":"Paxinos G , Franklin KBJ (2004) The mouse brain in stereotaxic coordinates, Ed 2. Amsterdam: Academic."},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurad.2020.09.009"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.52","doi-asserted-by":"publisher","DOI":"10.1016\/0376-8716(93)90032-L"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.53","doi-asserted-by":"publisher","DOI":"10.1093\/jbcr\/irz122"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.09.021"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108362"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.56","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2020173118"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.026"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.58","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-013-8516-5"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.59","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(01)00469-3"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.60","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-004-0350-x"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2021.100294"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.05.004"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2019.11.010"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.64","doi-asserted-by":"publisher","DOI":"10.1038\/s41372-022-01335-3"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.65","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-022-01376-4"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108005"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.02.006"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.68","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.3411"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.69","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2014.05.040"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.70","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2015.07.001"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.71","doi-asserted-by":"publisher","DOI":"10.1111\/ajad.12483"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.72","doi-asserted-by":"publisher","DOI":"10.1111\/apa.12210"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.73","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2018.4550"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.74","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200130109"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.75","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.02.058"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.76","unstructured":"Wei T , Simko V , Levy M (2021) corrplot: visualization of a correlation matrix. Vienna: R Foundation for Statistical Computing."},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.77","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.90"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.78","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(79)90063-7"},{"key":"2023041302170881000_9.5.ENEURO.0238-22.2022.79","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3641"}],"container-title":["eneuro"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/ENEURO.0238-22.2022","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/ENEURO.0238-22.2022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T10:21:01Z","timestamp":1681381261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eneuro.org\/lookup\/doi\/10.1523\/ENEURO.0238-22.2022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9]]},"references-count":79,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,10,3]]},"published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1523\/ENEURO.0238-22.2022"],"URL":"https:\/\/doi.org\/10.1523\/eneuro.0238-22.2022","relation":{},"ISSN":["2373-2822"],"issn-type":[{"value":"2373-2822","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9]]}}}