A New Animal Model for Acute Exercise Load Utilizing “Running Neuron” Stimulation

Abstract

1746 Non-athletes often suffer from muscle pain and fatigue after unaccustomed exercise. A lack of appropriate animal models makes difficult to analyze experimentally the muscle damage during acute exercise. We have reported that hyper-running behavior was inducible in rats by stimulating the “running neurons” residing in the ventromedial nucleus of the hypothalamus (VMH) with bicuculline methiodide (BMI), an antagonist to GABAA receptor. This VMH stimulation induced stereotypical running irrespective of the intention. Hence, it is feasible to set up a model for acute exercise by utilizing this hyper-running behavior. PURPOSE: To evaluate this VMH stimulation as a method to study muscle damage and fatigue in non-athletes. METHODS: At 7-weekold, male Wistar rats were assigned to two groups: the trained (n = 24) and the untrained rats (n = 25). The trained or the untrained were housed in cages with or without a running wheel, respectively, so that only the trained could run as they wished. At 8- week-old, a stainless steel guide cannula was stereotaxically inserted into the VMH. At 9-week-old, hyper-running was induced by injecting 0.5μl of BMI (500μM). After this induced running, plasma creatine phosphokinase (CPK) activity and the food intake were measured. RESULTS: When the VMH was stimulated by BMI, 12 trained and 11 untrained rats exhibited hyper-running behavior by exceeding the limit of the normal running behavior (total running time (TRT) <27min, maximum speed (MS) <16m/min, and total running distance (TRD) < 251m). In hyper-running 12 trained rats, TRT, MS, and TRD were 45.7 ± 4.0min, 43.8 ± 2.6m/min, and 727.6 ± 82.9m, respectively. In hyperrunning 11 untrained rats, TRT, MS, and TRD were 44.0 ± 3.2min, 31.5 ± 1.9m/min, and 502.4 ± 34.4m, respectively. Plasma CPK activities in both groups were elevated above the resting levels after the hyper-running. The increase was much greater (P ≤ 0.05) in the untrained (2.0-fold increase in the trained and 5.9-fold in the untrained after two hrs). Post-exercise food intake was reduced in both groups, and the reduction was larger (P ≤ 0.01) in the untrained (−36% in untrained and −13% in the trained). CONCLUSIONS: When hyper-running behavior of trained and untrained rats was compared, untrained rats ran more slowly (P≤ 0.01) and shorter distance (P ≤ 0.05) with nearly identical running time. However, it was evident that both muscle damage (plasma CPK activity) and exercise-induced fatigue (post-exercise food intake) were more severe in untrained rats. Therefore, the VMH stimulation is an appropriate model to study muscle damage and fatigue resulting from acute exercise, particularly with non-athletes.