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Childhood maltreatment is associated with increased severity of substance use disorder and frequency of relapse to drug use following abstinence. More...

Childhood maltreatment is associated with increased severity of substance use disorder and frequency of relapse to drug use following abstinence. However, the molecular and neurobiological substrates engaged during early traumatic events and mediating the relapse risk are poorly understood. Here, we show that the exposure to an adverse/hostile social experience in juvenile mice (social stressed mice, SS) influences the propensity to reinstate cocaine seeking after withdrawal periods. This effect is associated with an increased blood coagulation and a pauperization of brain vasculature. Moreover, a treatment with an anticoagulant agent during withdrawal abolishes the susceptibility to reinstate cocaine seeking in SS mice. These findings for the first time propose a molecular mechanism contributing to the increased susceptibility to relapse into cocaine abuse observed in individuals who had experienced childhood maltreatment. To analyze global gene expression differences between mice experiencing an hostile/adverse social environment during the third postnatal week and juvenile social isolated (SI) mice during cocaine abstinence. Peripheral Blood Mononuclear Cells were measured with Agilent mouse gene expression microarray during cocaine abstince after undergoing cocaine-seeking behavior studies by conditioned place preference test, extinction and withdrawal. Blood was collected 24 hours after the extinction test and genome-wide Overall design: PBMC of mice that experienced hostile/adverse social environment during the third postnatal week (SS) (n = 8) and mice that were juvenile social isolated (SI) (n = 6) were compared during cocaine abstinence. In particular mice were first conditioned with under-threshold cocaine dosage (5 mg/kg), then underwent extinction and withdrawal. 24 hours after withdrawal blood samples were taken and RNA from PBMC was analyzed on Agilent One-color experiments Less...