Social threat exposure in juvenile mice promotes cocaine‐seeking by altering blood clotting and brain vasculature

• DOI: 10.1111/adb.12373
• Publication Date: 2016-02-12T15:49:06Z
• Authors: Luisa Lo Iacono; Alessandro Valzania; Federica Visco‐Co...; Eleonora Aricò; Maria Teresa Viscomi; Luciano Castiello; Diego Oddi; Francesca R. D'Amato; Elisa Bisicchia; Olga Ermakova; Stefano Puglisi‐A...; Valeria Carola
• Keywords: Male; 0301 basic medicine; relapse risk factors; acetylsalicylic acid; blood coagulation; brain vasculature; childhood maltreatment; cocaine; relapse risk factors; VWF; medicine (miscellaneous); psychiatry and mental health; pharmacology; Behavior, Animal; childhood maltreatment; cocaine; Brain; acetylsalicylic acid; 3. Good health; blood coagulation; Cocaine-Related Disorders; Disease Models, Animal; Mice; 03 medical and health sciences; Preclinical Study; Cocaine; Mice, Inbred DBA; Animals; brain vasculature; vWF; Social Behavior; Blood Coagulation; Stress, Psychological

AbstractChildhood 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.