Blast–related disinhibition and risk seeking in mice and combat Veterans: Potential role for dysfunctional phasic dopamine release
Mild traumatic brain injury (mTBI) caused by exposure to high explosives has been called the “signature injury” of the wars in Iraq and Afghanistan. There is a wide array of chronic neurological and behavioral symptoms associated with blast-induced mTBI. However, the underlying mechanisms are not we...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-10-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996117301328 |
| _version_ | 1818675859736756224 |
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| author | A.G. Schindler J.S. Meabon K.F. Pagulayan R.C. Hendrickson K.D. Meeker M. Cline G. Li C. Sikkema C.W. Wilkinson D.P. Perl M.R. Raskind E.R. Peskind J.J. Clark D.G. Cook |
| author_facet | A.G. Schindler J.S. Meabon K.F. Pagulayan R.C. Hendrickson K.D. Meeker M. Cline G. Li C. Sikkema C.W. Wilkinson D.P. Perl M.R. Raskind E.R. Peskind J.J. Clark D.G. Cook |
| author_sort | A.G. Schindler |
| collection | DOAJ |
| description | Mild traumatic brain injury (mTBI) caused by exposure to high explosives has been called the “signature injury” of the wars in Iraq and Afghanistan. There is a wide array of chronic neurological and behavioral symptoms associated with blast-induced mTBI. However, the underlying mechanisms are not well understood. Here we used a battlefield-relevant mouse model of blast-induced mTBI and in vivo fast-scan cyclic voltammetry (FSCV) to investigate whether the mesolimbic dopamine system contributes to the mechanisms underlying blast-induced behavioral dysfunction. In mice, blast exposure increased novelty seeking, a behavior closely associated with disinhibition and risk for subsequent maladaptive behaviors. In keeping with this, we found that veterans with blast-related mTBI reported greater disinhibition and risk taking on the Frontal Systems Behavior Scale (FrSBe). In addition, in mice we report that blast exposure causes potentiation of evoked phasic dopamine release in the nucleus accumbens. Taken together these findings suggest that blast-induced changes in the dopaminergic system may mediate aspects of the complex array of behavioral dysfunctions reported in blast-exposed veterans. |
| first_indexed | 2024-12-17T08:34:17Z |
| format | Article |
| id | doaj.art-92a32b7e9283453398cf002b991b12cd |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T08:34:17Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-92a32b7e9283453398cf002b991b12cd2022-12-21T21:56:31ZengElsevierNeurobiology of Disease1095-953X2017-10-011062334Blast–related disinhibition and risk seeking in mice and combat Veterans: Potential role for dysfunctional phasic dopamine releaseA.G. Schindler0J.S. Meabon1K.F. Pagulayan2R.C. Hendrickson3K.D. Meeker4M. Cline5G. Li6C. Sikkema7C.W. Wilkinson8D.P. Perl9M.R. Raskind10E.R. Peskind11J.J. Clark12D.G. Cook13Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, 98195, USA; Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USADepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, 98195, USA; Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USADepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, 98195, USA; Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USADepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, 98195, USA; Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USAGeriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USAGeriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USADepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, 98195, USA; Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USA; Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USAGeriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USADepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, 98195, USA; Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USA; Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USADepartment of Pathology, Center for Neuroscience and Regenerative Medicine, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USADepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, 98195, USA; Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USADepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, 98195, USA; Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USADepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, 98195, USAGeriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Pharmacology, University of Washington, Seattle, WA 98195, USA; Corresponding author at: Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108, USA.Mild traumatic brain injury (mTBI) caused by exposure to high explosives has been called the “signature injury” of the wars in Iraq and Afghanistan. There is a wide array of chronic neurological and behavioral symptoms associated with blast-induced mTBI. However, the underlying mechanisms are not well understood. Here we used a battlefield-relevant mouse model of blast-induced mTBI and in vivo fast-scan cyclic voltammetry (FSCV) to investigate whether the mesolimbic dopamine system contributes to the mechanisms underlying blast-induced behavioral dysfunction. In mice, blast exposure increased novelty seeking, a behavior closely associated with disinhibition and risk for subsequent maladaptive behaviors. In keeping with this, we found that veterans with blast-related mTBI reported greater disinhibition and risk taking on the Frontal Systems Behavior Scale (FrSBe). In addition, in mice we report that blast exposure causes potentiation of evoked phasic dopamine release in the nucleus accumbens. Taken together these findings suggest that blast-induced changes in the dopaminergic system may mediate aspects of the complex array of behavioral dysfunctions reported in blast-exposed veterans.http://www.sciencedirect.com/science/article/pii/S0969996117301328Traumatic brain injuryNoveltyDopamineBlastVeteranDisinhibition |
| spellingShingle | A.G. Schindler J.S. Meabon K.F. Pagulayan R.C. Hendrickson K.D. Meeker M. Cline G. Li C. Sikkema C.W. Wilkinson D.P. Perl M.R. Raskind E.R. Peskind J.J. Clark D.G. Cook Blast–related disinhibition and risk seeking in mice and combat Veterans: Potential role for dysfunctional phasic dopamine release Neurobiology of Disease Traumatic brain injury Novelty Dopamine Blast Veteran Disinhibition |
| title | Blast–related disinhibition and risk seeking in mice and combat Veterans: Potential role for dysfunctional phasic dopamine release |
| title_full | Blast–related disinhibition and risk seeking in mice and combat Veterans: Potential role for dysfunctional phasic dopamine release |
| title_fullStr | Blast–related disinhibition and risk seeking in mice and combat Veterans: Potential role for dysfunctional phasic dopamine release |
| title_full_unstemmed | Blast–related disinhibition and risk seeking in mice and combat Veterans: Potential role for dysfunctional phasic dopamine release |
| title_short | Blast–related disinhibition and risk seeking in mice and combat Veterans: Potential role for dysfunctional phasic dopamine release |
| title_sort | blast related disinhibition and risk seeking in mice and combat veterans potential role for dysfunctional phasic dopamine release |
| topic | Traumatic brain injury Novelty Dopamine Blast Veteran Disinhibition |
| url | http://www.sciencedirect.com/science/article/pii/S0969996117301328 |
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