Physical exercise improves motor performance in individuals with Parkinson's disease and elevates mood in those with depression. Although underlying factors have not been identified, clues arise from previous studies showing a link between cognitive benefits of exercise and increases in brain-derived neurotrophic factor (BDNF). Here, we investigated the influence of voluntary wheel-running exercise on BDNF levels in the striatum of young male wild-type (WT) mice, and on the striatal release of a key motor-system transmitter, dopamine (DA). Mice were allowed unlimited access to a freely rotating wheel (runners) or a locked wheel (controls) for 30 d. Electrically evoked DA release was quantified in ex vivo corticostriatal slices from these animals using fast-scan cyclic voltammetry. We found that exercise increased BDNF levels in dorsal striatum (dStr) and increased DA release in dStr and in nucleus accumbens core and shell. Increased DA release was independent of striatal acetylcholine (ACh), and persisted after a week of rest. We tested a role for BDNF in the influence of exercise on DA release using mice that were heterozygous for BDNF deletion (BDNF^+/–). In contrast to WT mice, evoked DA release did not differ between BDNF^+/– runners and controls. Complementary pharmacological studies using a tropomyosin receptor kinase B (TrkB) agonist in WT mouse slices showed that TrkB receptor activation also increased evoked DA release throughout striatum in an ACh-independent manner. Together, these data support a causal role for BDNF in exercise-enhanced striatal DA release and provide mechanistic insight into the beneficial effects of exercise in neuropsychiatric disorders, including Parkinson's, depression, and anxiety.

SIGNIFICANCE STATEMENT Exercise has been shown to improve movement and cognition in humans and rodents. Here, we report that voluntary exercise for 30 d leads to an increase in evoked DA release throughout the striatum and an increase in BDNF in the dorsal (motor) striatum. The increase in DA release appears to require BDNF, indicated by the absence of DA release enhancement with running in BDNF^+/– mice. Activation of BDNF receptors using a pharmacological agonist was also shown to boost DA release. Together, these data support a necessary and sufficient role for BDNF in exercise-enhanced DA release and provide mechanistic insight into the reported benefits of exercise in individuals with dopamine-linked neuropsychiatric disorders, including Parkinson's disease and depression.

体育锻炼可以改善帕金森病患者的运动表现，并改善抑郁症患者的情绪。尽管潜在因素尚未确定，但之前的研究提供了一些线索，表明运动的认知益处与脑源性神经营养因子（BDNF）增加之间存在联系。在这里，我们研究了自愿跑轮运动对年轻雄性野生型 (WT) 小鼠纹状体 BDNF 水平以及纹状体释放关键运动系统递质多巴胺 (DA) 的影响。允许小鼠在 30 天内无限制地接触自由旋转的轮子（跑步者）或锁定的轮子（控制装置）。使用快速扫描循环伏安法对这些动物的离体皮质纹状体切片中的电诱发 DA 释放进行定量。我们发现运动增加了背侧纹状体 (dStr) 中的 BDNF 水平，并增加了 dStr 以及伏核核和壳中的 DA 释放。 DA 释放的增加与纹状体乙酰胆碱 (ACh) 无关，并且在休息一周后持续存在。我们使用 BDNF 杂合子缺失 (BDNF ^+/- ) 的小鼠测试了 BDNF 在运动对 DA 释放影响中的作用。与 WT 小鼠相比，BDNF ^+/–跑步者和对照组之间诱发的 DA 释放没有差异。在 WT 小鼠切片中使用原肌球蛋白受体激酶 B (TrkB) 激动剂进行的补充药理学研究表明，TrkB 受体激活还以不依赖乙酰胆碱的方式增加整个纹状体诱发的 DA 释放。总之，这些数据支持 BDNF 在运动增强纹状体 DA 释放中的因果作用，并提供了运动对神经精神疾病（包括帕金森病、抑郁症和焦虑症）有益影响的机制见解。

意义声明运动已被证明可以改善人类和啮齿动物的运动和认知。在这里，我们报告说，30 天的自愿运动会导致整个纹状体诱发的 DA 释放增加，以及背侧（运动）纹状体中的 BDNF 增加。 DA 释放的增加似乎需要 BDNF，这通过在 BDNF ^+/–小鼠中跑步时不存在 DA 释放增强来表明。使用药理学激动剂激活 BDNF 受体也被证明可以促进 DA 的释放。总之，这些数据支持 BDNF 在运动增强的 DA 释放中发挥必要且充分的作用，并提供了有关运动对患有多巴胺相关神经精神疾病（包括帕金森病和抑郁症）的个体的报道益处的机制见解。