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Frontal traumatic brain injury in rats causes long-lasting impairments in impulse control that are differentially sensitive to pharmacotherapeutics and associated with chronic neuroinflammation.

Haar, Vonder, Lam, Frederick, Adams, Wendy, Riparip, Lara-Kirstie, Kaur, Sukhbir, Muthukrishna, Michael, Rosi, Susanna and Winstanley, Catharine (2016) Frontal traumatic brain injury in rats causes long-lasting impairments in impulse control that are differentially sensitive to pharmacotherapeutics and associated with chronic neuroinflammation. ACS Chemical Neuroscience. ISSN 1948-7193

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Identification Number: 10.1021/acschemneuro.6b00166

Abstract

Traumatic brain injury (TBI) affects millions yearly, and is increasingly associated with chronic neuropsychiatric symptoms. We assessed the long-term effects of different bilateral frontal controlled cortical impact injury severities (mild, moderate, severe) on the five-choice serial reaction time task, a paradigm with relatively independent measurements of attention, motor impulsivity and motivation. Moderately- and severely-injured animals exhibited impairments across all cognitive domains that were still evident 14 weeks post-injury, while mild-injured animals only demonstrated persistent deficits in impulse control. However, recovery of function varied considerably between subjects such that some showed no impairment (“TBI-resilient”), some demonstrated initial deficits that recovered (“TBI-vulnerable”) and some never recovered (“chronically-impaired”). Three clinically-relevant treatments for impulsecontrol or TBI, amphetamine, atomoxetine, and amantadine, were assessed for efficacy in treating injury-induced deficits. Susceptibility to TBI affected the response to pharmacological challenge with amphetamine. Whereas sham and TBI-resilient animals showed characteristic impairments in impulse control at higher doses, amphetamine had the opposite effect in chronically-impaired rats, improving task performance. In contrast, atomoxetine and amantadine reduced premature responding but increased omissions, suggesting psychomotor slowing. Analysis of brain tissue revealed that generalized neuroinflammation was associated with impulsivity even when accounting for the degree of brain damage. This is one of the first studies to characterize psychiatric-like symptoms in experimental TBI. Our data highlight the importance of testing pharmacotherapies in TBI models in order to predict efficacy, and suggest that neuroinflammation may represent a treatment target for impulse control problems following injury.

Item Type: Article
Official URL: http://pubs.acs.org/journal/acncdm
Additional Information: © 2016 American Chemical Society
Divisions: LSE
Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
Sets: Departments > Social Psychology
Date Deposited: 02 Sep 2016 13:42
Last Modified: 20 Oct 2019 02:29
URI: http://eprints.lse.ac.uk/id/eprint/67567

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