TY - JOUR
T1 - Social threat exposure in juvenile mice promotes cocaine-seeking by altering blood clotting and brain vasculature.
AU - Lo Iacono, Luisa
AU - Valzania, Alessandro
AU - Visco-Comandini, Federica
AU - Aricò, Eleonora
AU - Viscomi, Maria Teresa
AU - Castiello, Luciano
AU - Oddi, Diego
AU - D'Amato, Francesca R.
AU - Bisicchia, Elisa
AU - Ermakova, Olga
AU - Puglisi-Allegra, Stefano
AU - Carola, Valeria
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - blood coagulation
KW - blood coagulation
UR - http://hdl.handle.net/10807/132202
U2 - 10.1111/adb.12373
DO - 10.1111/adb.12373
M3 - Article
SN - 1355-6215
VL - 22
SP - 911
EP - 922
JO - Addiction Biology
JF - Addiction Biology
ER -