Social threat exposure in juvenile mice promotes cocaine‐seeking by altering blood clotting and brain vasculature. (12th February 2016)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Addiction biology. Volume 22:Number 4(2017)
• Page Start: 911
• Page End: 922
• Publication Date: 2016-02-12
• Subjects: acetylsalicylic acid -- blood coagulation -- brain vasculature -- childhood maltreatment -- cocaine -- relapse risk factors -- vWF; Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.12373
• Languages: English
• ISSNs: 1355-6215

Abstract

Abstract: 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. Abstract : This study provides novel insights into the mechanism by which childhood maltreatment heightens risk for relapse in cocaine‐dependent individuals. We modeled childhood maltreatment by exposing juvenile mice to a threatening social experience. This influenced the propensity to reinstate cocaine seeking after periods of withdrawal in adulthood. We found that this phenotype was associated with greater blood coagulation and impairments in brain microvasculature. Notably, treatment with an anticoagulant agent during withdrawal abolished the susceptibility to reinstate cocaine seeking in these mice.