VA San Diego Healthcare System, San Diego, CA, 92161, USA.
Department of Anesthesiology, University of California San Diego, La Jolla, CA, 92161, USA.
Behav Brain Res. 2020 Jan 13;377:112235. doi: 10.1016/j.bbr.2019.112235. Epub 2019 Sep 12.
Adult female rats show greater running output compared with age-matched male rats, and the midbrain dopaminergic system may account for behavioral differences in running output. However, it is unknown if the lower running output in adult males can be regulated by wheel running experience during adolescence, and whether wheel running experience during adolescence will diminish the sex differences in running output during adulthood. We therefore determined and compared the exercise output in adult male and female rats that either had initiated voluntary wheel running only during adulthood or during adolescence. Our results demonstrate that running output in adult males were significantly higher when running was initiated during adolescence, and this higher running output was not significantly different from females. Running output did not differ during adulthood in females when wheel running was initiated during adolescence or during adulthood. Higher running output in females was associated with reduced expression of tyrosine hydroxylase and hyperactivation of calcium/calmodulin-dependent protein kinase II (CaMKII) in the dorsal striatum. Notably, running during adolescence-induced higher exercise output in adult males was associated with hyperactivation of CaMKII in the dorsal striatum, indicating a mechanistic role for CaMKII in running output. Together, the present results indicate sexually dimorphic adaptive biochemical changes in the dorsal striatum in rats that had escalated running activity, and highlight the importance of including sex as a biological variable in exploring neuroplasticity changes that predict enhanced exercise output in a voluntary physical activity paradigm.
成年雌性大鼠的跑动输出比同龄雄性大鼠更大，中脑多巴胺能系统可能是跑动输出行为差异的原因。然而，尚不清楚成年雄性大鼠较低的跑动输出是否可以通过青春期的轮跑经验来调节，以及青春期的轮跑经验是否会减少成年期跑动输出的性别差异。因此，我们确定并比较了仅在成年期或青春期开始自愿轮跑的成年雄性和雌性大鼠的运动输出。我们的结果表明，当跑动是在青春期开始时，成年雄性大鼠的跑动输出明显更高，并且这种更高的跑动输出与雌性大鼠没有显著差异。当跑动是在青春期或成年期开始时，雌性大鼠在成年期的跑动输出没有差异。雌性大鼠的跑动输出较高与背侧纹状体中酪氨酸羟化酶表达减少和钙/钙调蛋白依赖性蛋白激酶 II（CaMKII）的过度激活有关。值得注意的是，青春期跑动引起的成年雄性大鼠更高的运动输出与背侧纹状体中 CaMKII 的过度激活有关，表明 CaMKII 在跑动输出中起作用。总之，这些结果表明，在跑动活动增加的大鼠的背侧纹状体中存在性别二态性的适应性生化变化，并强调在探索预测自愿体力活动范式中增强运动输出的神经可塑性变化时，将性别作为生物学变量的重要性。
