Sex-differences in catecholamine transporter expression in the rodent prefrontal cortex following repetitive mild traumatic brain injury and methylphenidate treatment.

Abstract

Irregular transmitter activity is theorized to underly impaired prefrontal cortex (PFC)-mediated executive functions following repetitive mild traumatic brain injury (rmTBI). The psychostimulant, methylphenidate (MPH), enhances catecholamine neurotransmission by blocking reuptake transporters and is used off-label to treat post-TBI executive dysfunction. Both rmTBI and MPH are known to independently alter catecholamine transporter levels. The present report evaluated the interactive effects of rmTBI and a sub-chronic therapeutic dose of MPH on expression levels of vesicular monoamine transporter-2 (VMAT2) and norepinephrine reuptake transporter (NET) within the medial, anterior cingulate, and orbitofrontal subregions of the PFC in both male and female rats. MPH failed to rescue, and in some cases exacerbated, rmTBI-induced reductions in VMAT2 and NET expression in males, whereas transporter expression was largely unaltered in females. These results suggest MPH treatment produces further protein-level perturbations of catecholaminergic activity that are proposed to underlie executive dysfunction in males, but negligible effects in females, following rmTBI.