Clark Peter J, Amat Jose, McConnell Sara O, Ghasem Parsa R, Greenwood Benjamin N, Maier Steven F, Fleshner Monika
Integrative Physiology, University of Colorado Boulder, 354 UCB, Boulder, CO, 80309, United States of America.
Department of Psychology & Neuroscience, University of Colorado Boulder, Muenzinger D244, 345 UCB, Boulder, CO, 80309, United States of America.
PLoS One. 2015 Nov 10;10(11):e0141898. doi: 10.1371/journal.pone.0141898. eCollection 2015.
Accumulating evidence from both the human and animal literature indicates that exercise reduces the negative consequences of stress. The neurobiological etiology for this stress protection, however, is not completely understood. Our lab reported that voluntary wheel running protects rats from expressing depression-like instrumental learning deficits on the shuttle box escape task after exposure to unpredictable and inescapable tail shocks (uncontrollable stress). Impaired escape behavior is a result of stress-sensitized serotonin (5-HT) neuron activity in the dorsal raphe (DRN) and subsequent excessive release of 5-HT into the dorsal striatum following exposure to a comparatively mild stressor. However, the possible mechanisms by which exercise prevents stress-induced escape deficits are not well characterized. The purpose of this experiment was to test the hypothesis that exercise blunts the stress-evoked release of 5-HT in the dorsal striatum. Changes to dopamine (DA) levels were also examined, since striatal DA signaling is critical for instrumental learning and can be influenced by changes to 5-HT activity. Adult male F344 rats, housed with or without running wheels for 6 weeks, were either exposed to tail shock or remained undisturbed in laboratory cages. Twenty-four hours later, microdialysis was performed in the medial (DMS) and lateral (DLS) dorsal striatum to collect extracellular 5-HT and DA before, during, and following 2 mild foot shocks. We report wheel running prevents foot shock-induced elevation of extracellular 5-HT and potentiates DA concentrations in both the DMS and DLS approximately 24 h following exposure to uncontrollable stress. These data may provide a possible mechanism by which exercise prevents depression-like instrumental learning deficits following exposure to acute stress.
来自人类和动物文献的越来越多的证据表明,运动可以减轻压力的负面影响。然而,这种压力保护的神经生物学病因尚未完全明确。我们实验室报告称,在暴露于不可预测且无法逃避的尾部电击(可控压力)后,自愿性轮转跑步可保护大鼠在穿梭箱逃避任务中不表现出类似抑郁的工具性学习缺陷。逃避行为受损是由于背侧中缝核(DRN)中应激敏感的血清素(5-HT)神经元活动,以及在暴露于相对温和的应激源后5-HT随后过度释放到背侧纹状体中所致。然而,运动预防应激诱导的逃避缺陷的可能机制尚未得到充分表征。本实验的目的是检验运动可减弱应激诱发的背侧纹状体中5-HT释放这一假设。还检查了多巴胺(DA)水平的变化,因为纹状体DA信号传导对工具性学习至关重要,并且可能受到5-HT活动变化的影响。将成年雄性F344大鼠饲养6周,一组有转轮,一组没有,然后对其进行尾部电击或让它们在实验室笼子中不受干扰。24小时后,在背侧纹状体的内侧(DMS)和外侧(DLS)进行微透析,以在2次轻度足部电击之前、期间和之后收集细胞外5-HT和DA。我们报告称,轮转跑步可防止足部电击诱导的细胞外5-HT升高,并在暴露于可控压力后约24小时增强DMS和DLS中的DA浓度。这些数据可能提供了一种运动预防急性应激后类似抑郁的工具性学习缺陷的可能机制。