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 cocaineseeking
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
