Traumatic Brain Injury Induces Neuroinflammation and Neuronal Degeneration That Is Associated With Escalated Alcohol Self-Administration in Rats

Behav Brain Res. 2015 Feb 15;279:22-30. doi: 10.1016/j.bbr.2014.10.053. Epub 2014 Nov 10.


Background: Traumatic brain injury (TBI) affects millions of people each year and is characterized by direct tissue injury followed by a neuroinflammatory response. The post-TBI recovery period can be associated with a negative emotional state characterized by alterations in affective behaviors implicated in the development of Alcohol Use Disorder in humans. The aim of this study was to test the hypothesis that post-TBI neuroinflammation is associated with behavioral dysfunction, including escalated alcohol intake.

Methods: Adult male Wistar rats were trained to self-administer alcohol prior to counterbalanced assignment into naïve, craniotomy, and TBI groups by baseline drinking. TBI was produced by lateral fluid percussion (LFP; >2 ATM; 25ms). Alcohol drinking and neurobehavioral function were measured at baseline and following TBI in all experimental groups. Markers of neuroinflammation (GFAP and ED1) and neurodegeneration (FJC) were determined by fluorescence histochemistry in brains excised at sacrifice 19 days post-TBI.

Results: The cumulative increase in alcohol intake over the 15 days post-TBI was greater in TBI animals compared to naïve controls. A higher rate of pre-injury alcohol intake was associated with a greater increase in post-injury alcohol intake in both TBI and craniotomy animals. Immediately following TBI, both TBI and craniotomy animals exhibited greater neurobehavioral dysfunction compared to naïve animals. GFAP, IBA-1, ED1, and FJC immunoreactivity at 19 days post-TBI was significantly higher in brains from TBI animals compared to both craniotomy and naïve animals.

Conclusions: These results show an association between post-TBI escalation of alcohol drinking and marked localized neuroinflammation at the site of injury. Moreover, these results highlight the relevance of baseline alcohol preference in determining post-TBI alcohol drinking. Further investigation to determine the contribution of neuroinflammation to increased alcohol drinking post-TBI is warranted.

Keywords: Alcohol; Anxiety; Neuroinflammation; Self-administration; Traumatic brain injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / physiopathology*
  • Animals
  • Brain Injuries / complications*
  • Brain Injuries / pathology
  • Brain Injuries / psychology*
  • Encephalitis / etiology*
  • Encephalitis / metabolism
  • Ethanol
  • Male
  • Neurons / pathology
  • Rats
  • Rats, Wistar
  • Self Administration


  • Ethanol