INTRODUCTION. Current evidence suggests that early life growth restriction reduces physical activity engagement. Therefore, the purpose of this investigation was to examine the effects of early life growth-restriction on levels of wheel running in mice, and determine if known biological mechanisms regulate physical activity engagement. METHODS. Using a cross-fostering, protein-restricted nutritive model, mice were growth-restricted during either gestation (GUN; N = 3 litters) or postnatal life (PUN; N = 3 litters), along with a well fed control group (CON; N = 3 litters). At 21 days of age, all mice pups were weaned and fed a non-restrictive healthy diet for the remainder of the study. At 45 days of age mice were individually housed in cages with free moving running wheels to assess physical activity engagement. At day 70, mice were euthanized, and the nucleus accumbens was analyzed for dopamine receptor 1 expression. Skeletal muscle fiber type and cross-sectional area of the soleus, extensor digitorom longus, and diaphragm were analyzed by immunohistochemistry. The soleus from the other hind leg was evaluated for calsequestrin 1 and annexin A6 expression. RESULTS. The PUN female mice had a reduction (P = 0.0221) in wheel revolutions per day as compared to the GUN and CON females. PUN female mice also expressed significantly higher Drd1(P = 0.0247) and Casq1 (P = 0.0398) compared to the other groups. CONCLUSION. Growth-restriction during lactation reduced physical activity in female mice by reducing the central drive to be active and displayed a more fatigable skeletal muscle phenotype.
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