title: Social threat exposure in juvenile mice promotes cocaine-seeking by altering blood clotting and brain vasculature.
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.
authors: IRCSS Fondazione Santa Lucia Rome, Italy.
authors: Luisa
authors: L
authors: Lo Iacono
authors: IRCSS Fondazione Santa Lucia Rome, Italy.
authors: Alessandro
authors: A
authors: Valzania
authors: Sobell Department of Motor Neuroscience and Movement Disorders, UCL, London, UK.
authors: Federica
authors: F
authors: Visco-Comandini
authors: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: Eleonora
authors: E
authors: Aricò
authors: IRCSS Fondazione Santa Lucia Rome, Italy.
authors: Maria Teresa
authors: MT
authors: Viscomi
authors: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors: Luciano
authors: L
authors: Castiello
authors: Institute of Cellular Biology and Neurobiology, CNR, Rome, Italy.
authors: Diego
authors: D
authors: Oddi
authors: Institute of Cellular Biology and Neurobiology, CNR, Rome, Italy.
authors: Francesca R
authors: FR
authors: D'Amato
authors: IRCSS Fondazione Santa Lucia Rome, Italy.
authors: Elisa
authors: E
authors: Bisicchia
authors: Institute of Cellular Biology and Neurobiology, CNR, Rome, Italy.
authors: Olga
authors: O
authors: Ermakova
authors: IRCSS Fondazione Santa Lucia Rome, Italy.|Department of Psychology and 'Daniel Bovet' Center, University 'La Sapienza,' Rome, Italy.
authors: Stefano
authors: S
authors: Puglisi-Allegra
authors: IRCSS Fondazione Santa Lucia Rome, Italy.
authors: Valeria
authors: V
authors: Carola
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001777:Blood Coagulation / Q000502:physiology*; D001921:Brain / Q000098:blood supply*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012919:Social Behavior; D013315:Stress, Psychological / Q000150:complications* / Q000503:physiopathology
chemical_list: D003042:Cocaine
keywords: acetylsalicylic acid; blood coagulation; brain vasculature; childhood maltreatment; cocaine; relapse risk factors; vWF