Lo Iacono Luisa, Valzania Alessandro, Visco-Comandini Federica, Aricò Eleonora, Viscomi Maria Teresa, Castiello Luciano, Oddi Diego, D'Amato Francesca R, Bisicchia Elisa, Ermakova Olga, Puglisi-Allegra Stefano, Carola Valeria
IRCSS Fondazione Santa Lucia Rome, Italy.
Sobell Department of Motor Neuroscience and Movement Disorders, UCL, London, UK.
Addict Biol. 2017 Jul;22(4):911-922. doi: 10.1111/adb.12373. Epub 2016 Feb 12.
Childhood maltreatment is associated with increased severity of substance use disorder and frequent relapse to drug use following abstinence. However, the molecular and neurobiological substrates that are engaged during early traumatic events and mediate the greater risk of relapse are poorly understood and knowledge of risk factors is to date extremely limited. In this study, we modeled childhood maltreatment by exposing juvenile mice to a threatening social experience (social stressed, S-S). We showed that S-S experience influenced the propensity to reinstate cocaine-seeking after periods of withdrawal in adulthood. By exploring global gene expression in blood leukocytes we found that this behavioral phenotype was associated with greater blood coagulation. In parallel, impairments in brain microvasculature were observed in S-S mice. Furthermore, treatment with an anticoagulant agent during withdrawal abolished the susceptibility to reinstate cocaine-seeking in S-S mice. These findings provide novel insights into a possible molecular mechanism by which childhood maltreatment heightens the risk for relapse in cocaine-dependent individuals.
童年期受虐与物质使用障碍的严重程度增加以及戒断后频繁复吸毒品有关。然而，早期创伤事件中涉及的分子和神经生物学底物以及介导更高复发风险的机制仍知之甚少，而且迄今为止，风险因素的相关知识极其有限。在本研究中，我们通过将幼年小鼠暴露于威胁性社会经历（社会应激，S-S）来模拟童年期受虐。我们发现，S-S经历影响成年期戒断后恢复觅可卡因行为的倾向。通过探索血液白细胞中的全局基因表达，我们发现这种行为表型与更强的血液凝固有关。同时，在S-S小鼠中观察到脑微血管系统受损。此外，在戒断期间用抗凝剂治疗消除了S-S小鼠恢复觅可卡因行为的易感性。这些发现为童年期受虐增加可卡因依赖个体复发风险的可能分子机制提供了新的见解。
