The impact of psychological stressors on the progression of motor and non-motor disturbances observed in Parkinson's disease (PD) has received little attention. Given that PD likely results from many different environmental “hits”, we were interested in whether a chronic unpredictable stressor regimen would act additively or possibly even synergistically to augment the impact of the toxicant, paraquat, which has previously been linked to PD. Our findings support the contention that paraquat itself acted as a systemic stressor, with the pesticide increasing plasma corticosterone, as well as altering glucocorticoid receptor (GR) expression in the hippocampus. Furthermore, stressed mice that also received paraquat displayed synergistic motor coordination impairment on a rotarod test and augmented signs of anhedonia (sucrose preference test). The individual stressor and paraquat treatments also caused a range of non-motor (e.g. open field, Y and plus mazes) deficits, but there were no signs of an interaction (neither additive nor synergistic) between the insults. Similarly, paraquat caused the expected loss of substantia nigra dopamine neurons and microglial activation, but this effect was not further influenced by the chronic stressor. Taken together, these results indicate that paraquat has many effects comparable to that of a more traditional stressor and that at least some behavioral measures (i.e. sucrose preference and rotarod) are augmented by the combined pesticide and stress treatments. Thus, although psychological stressors might not necessarily increase the neurodegenerative effects of the toxicant exposure, they may promote co-morbid behaviors pathology.

心理应激因素对帕金森氏病（PD）中观察到的运动和非运动障碍的进展的影响很少受到关注。鉴于PD可能是由许多不同的环境“打击”造成的，因此我们对一种长期无法预测的应激方案是否会相加或什至协同作用来增强以前与PD相关的有毒物质百草枯的影响感兴趣。我们的发现支持以下论点：百草枯本身充当系统性应激源，该农药增加血浆皮质类固醇激素，并改变海马体中糖皮质激素受体（GR）的表达。此外，还接受百草枯的压力小鼠在旋转试验上表现出协同运动协调障碍，并表现出快感不足（蔗糖偏爱试验）。单独的压力和百草枯治疗也造成了一系列非运动性（例如开阔地域，Y和迷宫）缺陷，但是在这些侮辱之间没有相互作用的迹象（既无累加作用，也无协同作用）。同样，百草枯引起了黑质多巴胺神经元的预期损失和小胶质细胞活化，但这种作用并未受到慢性应激源的进一步影响。综上所述，这些结果表明百草枯具有许多与更传统的应激源相当的效果，并且农药和应激相结合的治疗至少增强了某些行为措施（即蔗糖偏爱和轮状动物）。因此，尽管心理压力源不一定会增加接触毒物的神经退行性作用，但它们可能会促进共病行为病理。