Cocaine self-administration is increased after frontal traumatic brain injury and associated with neuroinflammation

Cole Vonder Haar, Jacqueline Marie N. Ferland, Sukhbir Kaur, Lara Kirstie Riparip, Susanna Rosi, Catharine A. Winstanley

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Traumatic brain injury (TBI) has been linked to the development of numerous psychiatric diseases, including substance use disorder. However, it can be difficult to ascertain from clinical data whether the TBI is cause or consequence of increased addiction vulnerability. Surprisingly few studies have taken advantage of animal models to investigate the causal nature of this relationship. In terms of a plausible neurobiological mechanism through which TBI could magnify the risk of substance dependence, numerous studies indicate that TBI can cause widespread disruption to monoaminergic signaling in striatal regions, and also increases neuroinflammation. In the current study, male Long-Evans rats received either a mild or severe TBI centered over the frontal cortex via controlled cortical impact, and were subsequently trained to self-administer cocaine over 10 6-hour sessions. At the end of the study, markers of striatal dopaminergic function, and levels of inflammatory cytokine levels in the frontal lobes, were assessed via western blot and multiplex ELISA, respectively. There was significantly higher cocaine intake in a subset of animals with either mild or severe TBI. However, many animals within both TBI groups failed to acquire self-administration. Principal components analysis suggested that both dopaminergic and neuroinflammatory proteins were associated with overall cocaine intake, yet only an inflammatory component was associated with acquisition of self-administration, suggesting neuroinflammation may make a more substantial contribution to the likelihood of drug-taking. Should neuroinflammation play a causal role in mediating TBI-induced addiction risk, anti-inflammatory therapy may reduce the likelihood of substance abuse in TBI populations.

Original languageEnglish
Pages (from-to)2134-2145
Number of pages12
JournalEuropean Journal of Neuroscience
Issue number3
StatePublished - 1 Aug 2019
Externally publishedYes


  • brain injury
  • cytokine
  • dopamine
  • psychostimulant
  • rat


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