1613 - Catecholamine transporter protein levels within the rodent prefrontal cortex are altered by the interactions between repetitive mild traumatic brain injury and methylphenidate administration in a sex-dependent manner

Objectives: Aberrations of dopamine (DA) and norepinephrine (NE) function within the prefrontal cortex (PFC) following traumatic brain injury (TBI) lead to increased risky behavior. Our lab has shown that repeated mild TBI (rmTBI) sex-differentially increases risky behavior in rodents. Methylphenidate (MPH) is a psychostimulant drug used to treat Attention-Deficit Hyperactivity Disorder, also driven by a hypo-catecholaminergic PFC. MPH elevates catecholamine levels by blocking DA and NE transporters, DAT and NET. While psychostimulant use to treat post-TBI symptoms has been explored, effects of sub-chronic MPH on transporter levels following rmTBI have not. Our objective is to examine the effects of sub-chronic MPH use on NET and vesicular monoamine transporter 2 (VMAT2) levels in the PFC following rmTBI.

Design: A closed head-controlled cortical impact model was used to induce 3 mild injuries in Long Evans rats of both sexes. Rats received saline or MPH (2mg/kg) daily for 9 days (4 groups; sham/saline, sham/MPH, rmTBI/saline, rmTBI/MPH). Tissue from the medial (mPFC), orbitofrontal (OFC), and anterior cingulate cortex (ACC) regions of the PFC were collected. Western blotting protocols were used to measure NET and VMAT2 levels.

Results: Within the mPFC, female NET and VMAT levels decreased in the rmTBI/saline group, while the rmTBI/MPH group’s protein levels did not differ from controls. In males, mPFC VMAT levels decreased in both rmTBI groups. Within the OFC, NET and VMAT levels decreased in the male rmTBI/MPH group only. Similarly, ACC VMAT levels decreased in the male rmTBI/MPH group only.

Conclusions: These results suggest that rmTBI reduces transporter levels within the PFC, with sub-chronic MPH treatment possibly producing restorative benefits on these levels in female, but not male rodents following rmTBI. We conclude that interactions between rmTBI and MPH on catecholamine regulatory protein levels may begin to elucidate sex differential changes in behavior following injury and treatment.