Interactions Between Repetitive Mild Traumatic Brain Injury and Methylphenidate Administration on Catecholamine Transporter Protein Levels Within the Rodent Prefrontal Cortex
Anna Abrimian1, Eleni Papadopoulos1, Christopher Knapp1, Jessica Loweth1, Rachel Navarra1
1Department of Cell Biology and Neuroscience, Rowan-Virtua School of Translational Biomedical Engineering & Sciences, Stratford, NJ 08084
Objective:

To examine the effects of sub-chronic methylphenidate (MPH) use on norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) levels in the prefrontal cortex (PFC) following traumatic brain injury (TBI).

Background:

It is theorized that low concentrations of dopamine (DA) and norepinephrine (NE) within the PFC following TBI leads to increased risky behavior. Our lab has shown that repeated mild TBI (rmTBI) sex-differentially increases risky behavior in a rodent model. MPH is a psychostimulant drug used to treat symptoms of 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 the potential of psychostimulants to treat post-TBI symptoms have been explored, the effects of sub-chronic MPH on transporter levels following rmTBI has not.

Design/Methods:

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 7 days (4 groups; sham/saline, sham/MPH, rmTBI/saline, rmTBI/MPH). Brain tissue from the medial (mPFC) and orbitofrontal (OFC) regions of the PFC were collected and standard western blotting protocols were used to measure NET and VMAT2 levels.

Results:

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

Conclusions:

These results suggest that rmTBI reduces transporter levels within regions of the PFC and that sub-chronic MPH treatment may produce 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 risk-taking behavior following injury and treatment.

10.1212/WNL.0000000000205628