title: Experimental traumatic brain injury induces a pervasive hyperanxious phenotype in rats.
abstract: Mood disturbances, including depression and anxiety disorders, are common and disabling long-term sequelae of traumatic brain injury (TBI). These psychiatric conditions have generally been considered psychosocial consequences of the trauma, but neurobiological alterations and causes have also been implicated. Using a rat model of TBI (lateral fluid-percussion injury), this longitudinal study seeks to assess anxiety and depression-like behaviors following experimental TBI. Male Wistar rats (n = 20) received a severe (approximately 3.5 atmosphere) pressure pulse directed to the right sensorimotor cortex, or sham surgery (n = 15). At 1, 3, and 6 months following injury, all rats underwent four assessments of anxiety and depression-like behaviors: exposure to an open field, elevated plus maze test, the forced swim test, and the sucrose preference test. Injured animals displayed increased anxiety-like behaviors throughout the study, as evidenced by reduced time spent (p = 0.014) and reduced entries (p < 0.001) into the center area of the open field, and reduced proportion of time in the open arms of the plus maze (p = 0.015), compared to sham-injured controls. These striking changes were particularly evident 1 and 3 months after injury. No differences were observed in depression-like behaviors in the forced swim test (a measure of behavioral despair) and the sucrose preference test (a measure of anhedonia). This report provides the first evidence of persistent anxiety-like disturbances in an experimental model of TBI. This finding indicates that the common occurrence of these symptoms in human sufferers is likely to have, at least in part, a neurobiological basis. Studies in this model could provide insight into the mechanisms underlying affective disturbance in brain-injured patients.
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia. ncjones@unimelb.edu.au
authors.forename: Nigel C
authors.initials: NC
authors.lastname: Jones
authors.forename: Lisa
authors.initials: L
authors.lastname: Cardamone
authors.forename: John P
authors.initials: JP
authors.lastname: Williams
authors.forename: Michael R
authors.initials: MR
authors.lastname: Salzberg
authors.forename: Damian
authors.initials: D
authors.lastname: Myers
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000523:psychology*; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000473:pathology / Q000523:psychology*; D003863:Depression / Q000523:psychology; D018450:Disease Progression; D005518:Food Preferences / Q000523:psychology; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009068:Movement / Q000502:physiology; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose; D013550:Swimming / Q000523:psychology
chemical_list: D013395:Sucrose