title: Factors affecting increased risk for substance use disorders following traumatic brain injury: What we can learn from animal models.
abstract: Recent studies have helped identify multiple factors affecting increased risk for substance use disorders (SUDs) following traumatic brain injury (TBI). These factors include age at the time of injury, repetitive injury and TBI severity, neurocircuits, neurotransmitter systems, neuroinflammation, and sex differences. This review will address each of these factors by discussing 1) the clinical and preclinical data identifying patient populations at greatest risk for SUDs post-TBI, 2) TBI-related neuropathology in discrete brain regions heavily implicated in SUDs, and 3) the effects of TBI on molecular mechanisms that may drive substance abuse behavior, like dopaminergic and glutamatergic transmission or neuroimmune signaling in mesolimbic regions of the brain. Although these studies have laid the groundwork for identifying factors that affect risk of SUDs post-TBI, additional studies are required. Notably, preclinical models have been shown to recapitulate many of the behavioral, cellular, and neurochemical features of SUDs and TBI. Therefore, these models are well suited for answering important questions that remain in future investigations.
authors.affiliation: Department of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Substance Abuse Research, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Merkel
authors.affiliation: Department of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Substance Abuse Research, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Lee Anne
authors.initials: LA
authors.lastname: Cannella
authors.affiliation: Department of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Roshanak
authors.initials: R
authors.lastname: Razmpour
authors.affiliation: Department of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Lutton
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Raghupathi
authors.affiliation: Department of Pharmacology, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Substance Abuse Research, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Rawls
authors.affiliation: Department of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Shriners Hospitals Pediatric Research Center, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Substance Abuse Research, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA. Electronic address: servio@temple.edu.
authors.forename: Servio H
authors.initials: SH
authors.lastname: Ramirez
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic; D006801:Humans; D023421:Models, Animal; D012306:Risk; D019966:Substance-Related Disorders
keywords: Preclinical modeling; Substance use disorders; Traumatic brain injury