title: Frontal Traumatic Brain Injury Increases Impulsive Decision Making in Rats: A Potential Role for the Inflammatory Cytokine Interleukin-12.
abstract: Traumatic brain injury (TBI) is associated with the development of numerous psychiatric diseases. Of particular concern for TBI patients is the impact of chronic impulsivity on daily functioning. Despite the scope of the human problem, little has been done to address impulsivity in animal models of brain injury. In the current study, we examined the effects of either a severe or a milder bilateral frontal controlled cortical impact injury on impulsivity using the Delay Discounting Task (DDT), in which preference for smaller-sooner over larger-later rewards is indicative of greater impulsive choice. Both milder and severe TBI caused a significant, chronic increase in impulsive decision making. Despite these pronounced changes in performance of the DDT, memory function, as assessed by the Morris Water Maze, was not impaired in more mildly injured rats and only transiently impacted in the severe TBI group. Whereas a significant lesion was only evident in severely injured rats, analysis of cytokine levels within the frontal cortex revealed a selective increase in interleukin (IL)-12 that was associated with the magnitude of the change in impulsive choice caused by both milder and severe TBI. These findings suggest that tissue loss alone cannot explain the increased impulsivity observed, and that inflammatory pathways mediated by IL-12 may be a contributing factor. The findings from this study highlight the sensitivity of sophisticated behavioral measures designed to assess neuropsychiatric dysfunction in the detection of TBI-induced cognitive impairments and their utility in identifying potential mechanistic pathways and therapeutic targets.
authors.affiliation: 1 Djavad Mowafaghian Centre for Brain Health, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Cole
authors.initials: C
authors.lastname: Vonder Haar
authors.affiliation: 1 Djavad Mowafaghian Centre for Brain Health, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Kris M
authors.initials: KM
authors.lastname: Martens
authors.affiliation: 2 Brain and Spinal Injury Center, Departments of Physical Therapy Rehabilitation Science and Neurological Surgery, University of California San Francisco , San Francisco, California.
authors.forename: Lara-Kirstie
authors.initials: LK
authors.lastname: Riparip
authors.affiliation: 2 Brain and Spinal Injury Center, Departments of Physical Therapy Rehabilitation Science and Neurological Surgery, University of California San Francisco , San Francisco, California.
authors.forename: Susanna
authors.initials: S
authors.lastname: Rosi
authors.affiliation: 1 Djavad Mowafaghian Centre for Brain Health, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Wellington
authors.affiliation: 1 Djavad Mowafaghian Centre for Brain Health, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Catharine A
authors.initials: CA
authors.lastname: Winstanley
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D000070642:Brain Injuries, Traumatic / Q000150:complications* / Q000473:pathology* / Q000523:psychology; D003657:Decision Making; D005625:Frontal Lobe / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D007175:Impulsive Behavior; D018664:Interleukin-12 / Q000378:metabolism*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D018664:Interleukin-12
keywords: cognitive function; controlled cortical impact; cytokines; delay discounting; frontal cortex; inflammation