Effects of intrinsic aerobic capacity and ovariectomy on voluntary wheel running and nucleus accumbens dopamine receptor expression

Young-Min Park et. al

Physiology and Behavior

           

As mentioned in the last blog paper, there is a high incidence of cardiovascular disease in post-menopausal women. The current paper states that this is partially due to an increase in physical inactivity in post-menopausal women. Many studies have shown that increasing physical activity leads to a decreased risk of many diseases and so this decrease in physical activity in post-menopausal women is particularly interesting. What is the cause of the physical activity? Is it due to in inability to exercise as much, or maybe a decreased motivation for voluntary exercise? Rats can be selectively bred for high (HCR) and low (LCR) capacity running and these two different breeds show differing amount of voluntary wheel running. The mesolimbic dopamine system in the brain has been implicated in this motivation.

In the current paper rats were selectively bred for HCR and LCR which reflects their ability to exercise. Rats were kept on a 12:12 light dark cycle and then were randomized into four groups: HCR sham, HCR OVX, LCR sham, and LCR OVX (OVX is ovariectomy, sham is sham surgery). At 27 weeks surgeries were performed, either sham or ovariectomy, and then all rats were given access to a cage with a running wheel and running distance was monitored for 11 weeks. This was measured weekly (so variations due to the hormones were not seen on a daily basis as we do in our lab). After this period of 11 weeks the rats were sacrificed, and brain tissue was harvested for analysis. mRNA was extracted from the nucleus accumbens tissue that was harvested and levels of D1 like receptors, D2 like receptor and the dopamine transporter (DAT) were all measured.

As expected the high capacity group ran more throughout the entire 11 week period as compared to the low capacity group. In both ovariectomy groups running was reduced at all 11 weeks compared to the correlated sham group. It was also found that the high capacity group had a greater ovariectomy induced reduction in the amount of weekly running than the low capacity group. As for the general trend of running within each group, all groups did increase their running throughout the experiment with the exception of the high capacity ovariectomy group which actually decreased their running throughout 11 weeks of the experiment. In gene expression analysis it was found that the HCR group had greater excitatory dopamine expression than the LCR group and that inhibitory dopamine gene expression was actually greater in the LCR group than the HCR group. There were interesting finding in expression when looking at the different in ovariectomy groups. OVX increased the amount of inhibitory dopamine expression in the HCR group, but in the LCR group, OVX, decreased the amount of dopamine expression. In this paper the estimation of dopamine activation was the ratio of excitatory dopamine expression vs. inhibitory dopamine expression. When this was assessed it was found that this ratio was greater in HCR compared to LCR and that OVX only affected this ratio in the HCR group. This ratio was also positively correlated with weekly running distances across all of the groups.

The findings of this paper are very interesting. It is interesting to see that the high capacity group did not protect against the decrease in voluntary wheel running in the OVX group. I think that It would be extremely interesting to get at the mechanisms that the female hormones work by in the brain that cause these behavioral changes in the rats. This could result in possible therapeutic interventions in post-menopausal women that could help decrease the incidence of cardiovascular disease in these women.

- BeN RoShAk