Gender and environmental enrichment impact dopamine transporter expression after experimental traumatic brain injury

Abstract

Dopamine (DA) systems are implicated in cognitive deficits following traumatic brain injury (TBI). Rodent studies have demonstrated that both environmental enrichment (EE) and sex hormones can influence DA systems. The dopamine transporter (DAT) plays a crucial role in regulating DA transmission, and previous work shows that DAT is decreased after TBI in males. Therefore, the purpose of this study was to examine the effects of gender and EE on frontal cortex and striatal DAT expression after TBI. Sprague–Dawley male ( n = 24) and cycling female rats ( n = 24) were placed into EE or standard housing after controlled cortical impact (2.7 mm, 4.0 m/s) injury or sham surgery (eight groups, n = 6/group). Four weeks post-surgery, bilateral frontal cortex and striatal DAT expression was examined via Western blot. Results demonstrated that there was a significant effect of injury, EE, and region on DAT expression ( P < 0.05 all comparisons) on female groups. There were no significant DAT decreases in any region as a result of injury, however, EE did promote significant post-injury DAT decreases in the striatum and ipsilateral frontal cortex ( P < 0.05 all comparisons) compared to female shams housed in the standard environment. For males, there was a significant effect of injury, EE, and region for male groups ( P < 0.05 all comparisons). There were decreases in DAT expression in three regions studied for injured males housed in the standard environment compared to sham males in the standard environment ( P < 0.05 all comparisons), however, EE did not add significantly to post-injury DAT decreases in these regions. These results suggest that CCI causes larger relative decreases in DAT expression for males compared to females and that treatment with EE has larger effects on post-injury DAT expression for females than males. These findings may have some relevance to treatment paradigms using dopaminergic neurostimulants after TBI.