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

L. Lo Iacono, A. Valzania, F. Visco-Comandini, E. Aricò, M.T. Viscomi, L. Castiello, D. Oddi, F.R. D'Amato, E. Bisicchia, O. Ermakova, S. Puglisi-Allegra, V. Carola

Research output: Contribution to journalArticle

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. © 2016 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.
Original languageEnglish
Pages (from-to)911-922
Number of pages12
JournalAddiction Biology
Volume22
Issue number4
DOIs
Publication statusPublished - 2017

Keywords

  • acetylsalicylic acid
  • blood coagulation
  • brain vasculature
  • childhood maltreatment
  • cocaine
  • relapse risk factors
  • vWF
  • anticoagulant agent
  • adulthood
  • animal experiment
  • animal model
  • Article
  • blood clotting
  • brain blood vessel
  • cocaine dependence
  • controlled study
  • environmental exposure
  • female
  • gene expression
  • juvenile
  • leukocyte
  • male
  • mouse
  • nonhuman
  • phenotype
  • priority journal
  • relapse
  • social stress
  • threat

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    Lo Iacono, L., Valzania, A., Visco-Comandini, F., Aricò, E., Viscomi, M. T., Castiello, L., Oddi, D., D'Amato, F. R., Bisicchia, E., Ermakova, O., Puglisi-Allegra, S., & Carola, V. (2017). Social threat exposure in juvenile mice promotes cocaine-seeking by altering blood clotting and brain vasculature. Addiction Biology, 22(4), 911-922. https://doi.org/10.1111/adb.12373