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In a genome\u2010wide methylation analysis, we recently identified an association of a methylated region in the\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">OPRL<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      gene with alcohol\u2010use disorders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we investigate the biological basis of this observation by analysing psychosocial stressors, methylation of the\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">OPRL<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      gene, brain response during reward anticipation and alcohol drinking in 660 fourteen\u2010year\u2010old adolescents of the\n                      <jats:styled-content style=\"fixed-case\">IMAGEN<\/jats:styled-content>\n                      study. We validate our findings in marchigian sardinian (msP) alcohol\u2010preferring rats that are genetically selected for increased alcohol drinking and stress sensitivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that low methylation levels in intron 1 of\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">OPRL<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      are associated with higher psychosocial stress and higher frequency of binge drinking, an effect mediated by\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">OPRL<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      methylation. In individuals with low methylation of\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">OPRL<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      , frequency of binge drinking is associated with stronger\n                      <jats:styled-content style=\"fixed-case\">BOLD<\/jats:styled-content>\n                      response in the ventral striatum during reward anticipation. In msP rats, we found that stress results in increased alcohol intake and decreased methylation of\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">OPRL<\/jats:styled-content>\n                      <\/jats:italic>\n                      1 in the nucleus accumbens.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings describe an epigenetic mechanism that helps to explain how psychosocial stress influences risky alcohol consumption and reward processing, thus contributing to the elucidation of biological mechanisms underlying risk for substance abuse.<\/jats:p>\n                  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