Repetitive but not single blast mild traumatic brain injury increases ethanol responsivity in mice and risky drinking behavior in combat Veterans

• DOI: 10.1101/2020.11.10.20229427
• Publication Date: 2020-11-13T17:35:19Z
• Authors: Abigail G. Schindler; Britahny Baskin; Barbara Juarez; Suhjung Janet Lee; Rebecca Hendrickson; Katherine Pagulayan; Larry S. Zweifel; Murray A. Raskind; Paul E.M. Phillips; Elaine R. Peskind; David G. Cook
• Keywords: Sensation Seeking; Irritability

ABSTRACT Mild traumatic brain injury (mTBI) is common in civilians and highly prevalent among military Servicemembers contact sports athletes. mTBI, especially within populations, often comorbid with posttraumatic stress disorder (PTSD), can increase health-risk behaviors (e.g., sensation/novelty seeking, impulsivity, risk taking, irritability/aggression) substance misuse/abuse, but underlying mechanisms remain poorly understood. Using an established mouse model of blast here we examined the effects single (1x) repetitive (3x) exposure on ethanol responsivity using a battery tests, each associated distinct aspects alcohol abuse vulnerability. While both increased sedative properties high-dose (with no change tolerance or metabolism), only potentiated ethanol-induced locomotor stimulation shifted intake patterns (i.e., consumption ‘front-loading’) during intermittent two bottle choice. To establish translational relevance, next self-report responses to Alcohol Use Disorders Identification Test-Consumption Questions (AUDIT-C) used novel unsupervised machine learning approach investigate whether history acute symptoms mTBI affected drinking Iraq Afghanistan Veterans. AUDIT-C scores were Veterans subsequent cluster analysis identified three-cluster solution: ‘low’ (low low frequency), ‘frequent’ high ‘risky’ (high where displayed shift assignment from ‘risky’, as compared who deployed and/or had lifetime TBI. Together, these results offer new insight regarding how may give rise use/misuse highlight potential for adverse following exposure.