Voluntary running-wheel exercise decreases the threshold for rewarding intracranial self-stimulation

Abstract

Physical exercise has mood-enhancing and antidepressant properties although the mechanisms underlying these effects are not known. The present experiment investigated the effects of prolonged access to a running wheel on electrical self-stimulation of the lateral hypothalamus (LHSS), a measure of hedonic state, in rats. Rats with continuous voluntary access to a running wheel for either 2 or 5 weeks exhibited dramatic leftward shifts in the effective current 50 (ECu50; current value that supports half of maximum responding) of their LHSS current-response functions compared to their baselines, indicating a decrease in reward threshold, whereas control rats current-response functions after 2 or 5 weeks were not significantly different from baseline. An inverse correlation existed between the change in ECu50 from baseline and the amount an animal had run in the day prior to LHSS testing, indicating that animals that exhibited higher levels of running showed a more robust decrease in LHSS threshold. We conclude that long-term voluntary exercise increases sensitivity to rewarding stimuli, which may contribute to its antidepressant properties.

Figure 1

Five weeks of voluntary wheel running leads to a decrease in lateral hypothalamic self-stimulation reward threshold. (A) A representative current-response curve for one rat. Filled circles illustrate raw data points, and the solid line indicates the fit curve. (B) Average daily running distance for the 5-week high- (>0.5 km/day) and low-run (<0.5 km/day) groups. (C) Mean lateral hypothalamic self-stimulation (LHSS) current-response curves for 5-week locked-wheel control rats. Data are shown as sigmoid curves fit to mean values. Black dots indicate the midpoint effective current 50 (ECu₅₀) of each curve with corresponding vertical and horizontal SEM bars. (D) Mean LHSS current-response curves for animals in the high-run group (>0.5 km/day). (E) Mean ECu₅₀ values + SEM for the locked-wheel control group (n = 5), the high-run (>0.5 km/day; n = 8), and (C) low-run (<0.5 km/day; n = 4) 5-week exercise groups. The high-run group showed a decreased ECu₅₀ postexercise relative to their baseline value, whereas the low-run and locked-wheel groups were not significantly different from baseline. (F) Scatterplot and line of best fit depicting the relationship between change in ECu₅₀ values from baseline plotted against the distance animals ran (km/day) in the day prior to LHSS testing. ^* p < 0.05 vs. respective baseline value.

Figure 2

Two weeks of voluntary wheel running exercise decreases the threshold for LHSS that persists 1 week after withdrawal of the wheel. (A) Mean lateral hypothalamic self-stimulation (LHSS) current-response curves for 2-week locked-wheel control rats. (B) Mean lateral hypothalamic self-stimulation (LHSS) current-response curves for 2-week exercised rats showing a robust leftward shift following 2 weeks of wheel running (2 Week Wheel) that returns to baseline following 2 weeks with a locked wheel (2 Week Recover). (C) Mean ECu₅₀ values + SEM animals with access to a running wheel for 2 weeks. ECu₅₀ values were significantly lower than baseline following 2 weeks of wheel access (2-wk ex), remained lower than baseline after 1 week with a locked wheel (1-wk rec) before returning to baseline after 2 weeks with a locked wheel (2-wk rec). * p < 0.05 versus baseline value.