Concurrent chronic methamphetamine exposure may influence behavioral outcomes following repetitive mild traumatic brain injury

RATIONALE: Traumatic brain injury (TBI) and substance use disorder (SUD) share several characteristics, including neurological outcomes and pathological traits. Misuse of stimulants, both non-prescription use of medications and illicit use of methamphetamine, is rising. Despite potential for misuse, stimulants are prescribed as treatment for some TBI-induced symptoms. Given that 40% of TBI patients have a history of SUD prior to injury, studies of the role that chronic substance misuse plays on the deleterious outcomes of TBI are warranted. OBJECTIVES: Our study explores the role that chronic methamphetamine exposure plays in the acute and long-term behavioral outcomes of repetitive mild TBI (rmTBI). We hypothesized that chronic methamphetamine exposure would exacerbate the behavioral deficits induced by rmTBI. METHODS: We developed a model combining non-contingent dosing of methamphetamine with the Closed Head Model of Engineered Rotational Acceleration (CHIMERA). Behavioral assays were employed one month after the final TBI to assess short-term effects and were repeated six months following the final TBI for long-term effects. RESULTS: The Loss of Righting Reflex showed that chronic methamphetamine exposure impacted neither TBI severity nor immediate recovery. The T-maze and NORT revealed that rmTBI concurrent to chronic methamphetamine exposure induced short- and long-term cognitive deficits. Methamphetamine negatively impacted balance and coordination on the accelerated rotarod at the later timepoint only. CONCLUSIONS: Together, these findings suggest that chronic methamphetamine exposure could potentially increase long-term, but not acute, TBI-induced deficits.