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M. Keck Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Addiction vulnerability involves complex gene X environment interactions leading to a pathological response to drugs. Identification of the genes involved in these interactions is an important step in understanding the underlying neurobiology and rarely have such analyses examined sex\u2010specific influences. To dissect this interaction, we examined the impact of prenatal stress (PNS) on cocaine responsiveness in male and female mice of the BXD recombinant inbred panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>BXD strains were subjected to timed mating and assigned to PNS or control groups. PNS dams were subjected to restraint stress (1\u2010hr restraint, three times daily) starting between embryonic day (E) 11 and 14 and continued until parturition. Adult male and female, control and PNS offspring were tested for locomotor response to initial and repeated cocaine injections (sensitization) as well as cocaine\u2010induced conditioned place preference (CPP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Strain, PNS, and sex interacted to modulate initial and sensitized cocaine\u2010induced locomotion, as well as CPP. Moreover, a quantitative trait locus (QTL) interacting with PNS regulating initial locomotor response to cocaine (chromosome X, 37.91 to 50.95\u00a0Mb) was identified. Also PNS\u2010independent, female\u2010specific QTLs regulating CPP (chromosome 11, 65.50 to 81.31\u00a0Mb) and sensitized cocaine\u2010induced locomotion (chromosome 16, 95.79 to 98.32\u00a0Mb) were identified. Publicly available mRNA expression data were utilized to identify cis\u2010eQTL and transcript covariation with the behavioural phenotype to prioritize candidate genes; including <jats:italic>Aifm1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These QTL encompass genes that may moderate genetic susceptibility to PNS and interact with sex to determine adult responsiveness to cocaine and addiction vulnerability.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v176.21\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v176.21\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14661","type":"journal-article","created":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T11:28:56Z","timestamp":1552649336000},"page":"4159-4172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Discovery of early life stress interacting and sex\u2010specific quantitative trait loci impacting cocaine responsiveness"],"prefix":"10.1111","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9972-6498","authenticated-orcid":false,"given":"Jared R.","family":"Bagley","sequence":"first","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1078-1077","authenticated-orcid":false,"given":"Karen K.","family":"Szumlinski","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California"},{"name":"Neuroscience Research Institute University of California Santa Barbara  Santa Barbara California"},{"name":"Department of Molecular Cellular and Developmental Biology University of California Santa Barbara  Santa Barbara California"},{"name":"Institute for Collaborative Biotechnologies University of California Santa Barbara  Santa Barbara California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tod E.","family":"Kippin","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California"},{"name":"Neuroscience Research Institute University of California Santa Barbara  Santa Barbara California"},{"name":"Department of Molecular Cellular and Developmental Biology University of California Santa Barbara  Santa Barbara California"},{"name":"Institute for Collaborative Biotechnologies University of California Santa Barbara  Santa Barbara California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2012.54"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303591200"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13878"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13877"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/10253890.2011.586447"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.011163"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021404714631"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200104000-00009"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-009-1656-7"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2009.00525.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2012.00795.x"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2381"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2009.10.001"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/138.3.963"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2004.00079.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1137073"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-015-4147-z"},{"issue":"1","key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/genetics\/151.1.373","article-title":"Statistical methods for mapping quantitative trait loci from a dense set of markers","volume":"151","author":"Dupuis J.","year":"1999","journal-title":"Genetics"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-010-1916-6"},{"issue":"52","key":"e_1_2_11_21_1","article-title":"Prenatal stress alters progestogens to mediate susceptibility to sex\u2010typical, stress\u2010sensitive disorders, such as drug abuse: A review","volume":"2","author":"Frye C. 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