Altered dopaminergic profiles: implications for the regulation of voluntary physical activity

Abstract

The biological regulating factors of physical activity in animals are not well understood. This study investigated differences in the central mRNA expression of seven dopamine genes (Drd1, Drd2, Drd3, Drd4, Drd5, TH, and DAT) between high active C57/LJ (n=17) male mice and low active C3H/HeJ (n=20) male mice, and between mice with access to a running wheel and without running wheel access within strain. Mice were housed with running wheels interfaced with a computer for 21 days with distance and duration recorded every 24 h. On day 21, the striatum and nucleus accumbens were removed during the active period (approximately 9 pm) for dopaminergic analysis. On average, the C57L/J mice with wheels ran significantly farther (10.25+/-1.37 km/day vs. 0.01+/-0.09 km/day, p<0.001), longer (329.73+/-30.52 min/day vs. 7.81+/-6.32 min/day, p<0.001), and faster (31.27+/-3.13 m/min vs. 11.81+/-1.08 m/min, p<0.001) than the C3H/HeJ mice with wheels over the 21 day period. No differences in gene expression were found between mice in either strain with wheels and those without wheels suggesting that access to running wheels did not alter dopaminergic expression. In contrast, relative expression for two dopamine genes was significantly lower in the C57L/J mice compared to the C3H/HeJ mice. These results indicate that decreased dopaminergic functioning is correlated with increased activity levels in C57L/J mice and suggests that D1-like receptors as well as tyrosine hydroxylase (an indicator of dopamine production), but not D2-like receptors may be associated with the regulation of physical activity in inbred mice.

Figure 1

Average distance, duration, and speed for C57L/J (n=10) and C3H/HeJ (n=10) mice over 21 days. A. Average distance (Km/day) for C57L/J (10.25±1.37) and C3H/HeJ (0.01±0.09). B. Average duration (mins/day) for C57L/J (329.73±30.52) and C3H/HeJ (7.81±6.32) mice. C. Average speed (m/min) for C57L/J (31.27±3.13) and C3H/HeJ (11.81±1.08) mice. Standard deviations are reported * designates significantly higher than C3H/HeJ mice at p<0.001.

Figure 2

Gene expression in the striatum/nucleus accumbens tissue of C3H/HeJ mice housed with a running wheel and C3H/HeJ mice housed without a running wheel. No expression differences (p>0.05) were found between control (n=10) and running (n=10) C3H/HeJ mice for any of the seven dopaminergic genes. Standard deviations are reported.

Figure 3

Gene expression in the striatum/nucleus accumbens tissue of C57L/J mice housed with a running wheel and C57L/J mice housed without a running wheel. No expression differences (p>0.05) were found between control (n=7) and running (n=10) C57L/J mice for any of the seven dopaminergic genes. Standard deviations are reported.

Figure 4

A significant main effect of strain was found for two dopaminergic genes (Drd1, and Tyrosine Hydroxylase). For each of these genes, C57L/J mice had significantly lower expression than C3H/HeJ mice. Standard deviations are reported. p values are reported for each gene in the figure. * indicates significance at p<0.05.