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

Abstract

Irregular catecholamine 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. Although rmTBI and MPH have been shown 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 subregions of the PFC in both male and female rats. Treatment with MPH restored rmTBI-induced reductions in transporter expression in females. However, in males subjected to rmTBI, MPH exacerbated reductions in transporter expression within the PFC. These results suggest MPH treatment produces beneficial effects in females but exaggerates pathological outcomes in males when used to treat post-rmTBI symptoms.