Persistent Increased Anxiety-like Behaviour Following Experimental Traumatic Brain Injury in the Rat

  • Dr Lisa Cardamone, Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Australia
  • Nigel Jones, Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Australia
  • John Williams, Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Australia
  • Michael Salzberg, Department of Psychiatry, University of Melbourne, Australia
  • Damian Myers, Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Australia
  • Terence O'Brien, Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Australia
  • Objective: Mood disturbances, including elevated anxiety and depression, are common and disabling long-term sequelae of traumatic brain injury (TBI). These behaviours have been considered as psychological and social consequences of the trauma, but neurobiological alterations have also been implicated. This longitudinal study, using a rat model of TBI (fluid percussion injury), was designed to assess the anxiety- and depression-like behaviours post-TBI. Methods: Male Wistar rats (n=20) received a ~3.5 atm fluid pressure pulse delivered over the right sensorimotor cortex, or sham injury (n=15). At 1, 3 and 6 months following injury, rats underwent four assessments of anxiety and depression-like behaviours: elevated plus maze, open field test, forced swim test and sucrose-preference test. Results: Injured animals displayed increased anxiety-like behaviour as evidenced by reduced % time spent in open arms of the plus maze (p=0.001, two-way ANOVA), and reduced time spent (p=0.013, two-way ANOVA) and reduced entries (p<0.001, two-way ANOVA) into the center area of the open field. No differences were observed in depression-like behaviour in sucrose preference (a measure of anhedonia) or time spent immobile in the forced swim test (a measure of behavioural despair). Conclusion: This report provides the first evidence of persistent anxiety-like disturbances in a model of traumatic brain injury in rats. This finding indicates that the common occurrence of these symptoms in humans who have suffered a TBI is likely to have, in at least part, a neurobiological basis. Studies in this model could provide insights into the mechanisms underlying affective disorders in brain injured patients.