Kim Jinhee, Lim Juhee, Moon Seong-Hee, Liu Kwang-Hyeon, Choi Hyun Jin
College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam 13488, Republic of Korea.
BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
Biomol Ther (Seoul). 2020 May 1;28(3):282-291. doi: 10.4062/biomolther.2020.055.
Inhaled solvents such as toluene are of particular concern due to their abuse potential that is easily exposed to the environment. The inhalation of toluene causes various behavioral problems, but, the effect of short-term exposure of toluene on changes in emotional behaviors over time after exposure and the accompanying pathological characteristics have not been fully identified. Here, we evaluated the behavioral and neurochemical changes observed over time in mice that inhaled toluene. The mice were exposed to toluene for 30 min at a concentration of either 500 or 2,000 ppm. Toluene did not cause social or motor dysfunction in mice. However, increased anxiety-like behavior was detected in the short-term after exposure, and depression-like behavior appeared as delayed effects. The amount of striatal dopamine metabolites was significantly decreased by toluene, which continued to be seen for up to almost two weeks after inhalation. Additionally, an upregulation of serotonin 1A (5-HT) receptor in the hippocampus and the substantia nigra, as well as reduced immunoreactivity of neurogenesis markers in the dentate gyrus, was observed in the mice after two weeks. These results suggest that toluene inhalation, even single exposure, mimics early anxietyand delayed depression-like emotional disturbances, underpinned by pathological changes in the brain.
诸如甲苯之类的吸入性溶剂因其易暴露于环境中的滥用可能性而备受关注。吸入甲苯会引发各种行为问题，但是，甲苯短期暴露对暴露后随时间变化的情绪行为及伴随的病理特征的影响尚未完全明确。在此，我们评估了吸入甲苯的小鼠随时间推移所观察到的行为和神经化学变化。小鼠以500或2000 ppm的浓度暴露于甲苯中30分钟。甲苯未导致小鼠出现社交或运动功能障碍。然而，暴露后短期内检测到焦虑样行为增加，且抑郁样行为表现为延迟效应。甲苯使纹状体多巴胺代谢产物的量显著减少，吸入后长达近两周仍持续可见。此外，两周后在小鼠中观察到海马体和黑质中5-羟色胺1A（5-HT）受体上调，以及齿状回中神经发生标志物的免疫反应性降低。这些结果表明，即使单次暴露吸入甲苯，也会模拟早期焦虑和延迟的抑郁样情绪障碍，其基础是大脑的病理变化。
