Wayne State University, Department of Chemistry, Detroit, MI 48202, United States of America.
Wayne State University, Department of Psychology, Detroit, MI 48202, United States of America.
Toxicol Appl Pharmacol. 2020 Dec 1;408:115260. doi: 10.1016/j.taap.2020.115260. Epub 2020 Oct 2.
Intentionally inhaling volatile organic solvent like toluene for its intoxicating effects continues to be a public health concern. While repeated abuse of toluene has deleterious behavioral and health effects, little is known about the actions of toluene on the dopaminergic neurotransmitter system within the central nervous system.
The present study employed complementary neurochemical techniques of slice fast-scan cyclic voltammetry (FSCV) and in vivo microdialysis, to assess dopamine (DA) dynamics immediately after repeated exposure to 2000- or 4000-ppm toluene. DA D3 autoreceptor functionality, measured by FSCV with pharmacological manipulations and brain tissue content analysis with high performance liquid chromatography, were also used to account for the changes in the DA dynamics.
Toluene-exposed mice had decreased stimulated DA release only in the nucleus accumbens core immediately after seven days of repeated exposure. DA uptake was decreased in the core only after 2000-ppm exposure. The differences in stimulated DA release were not attributed to alterations in intraneuronal DA levels as measured by tissue content analysis. Basal extracellular DA levels were not significantly different between the air- and toluene-treated mice. However, following an additional toluene exposure, mice had elevated extracellular DA levels in the nucleus accumbens during recovery. This potentiation in extracellular accumbal DA levels was further heightened following potassium stimulation. The accumbal DA D3 autoreceptor function did not appear to play a role as a potential mediator for these differences.
Our FSCV and microdialysis results suggest a neuroadaptation in DA release mechanics within the nucleus accumbens, but the exact neuronal mechanism of toluene's impact remains elusive.
出于陶醉效果而故意吸入甲苯等挥发性有机溶剂仍然是一个公共卫生问题。虽然反复滥用甲苯会产生有害的行为和健康影响，但人们对甲苯在中枢神经系统中对多巴胺能神经递质系统的作用知之甚少。
本研究采用切片快速扫描循环伏安法（FSCV）和体内微透析等互补神经化学技术，评估重复暴露于 2000 或 4000 ppm 甲苯后立即的多巴胺（DA）动力学。还使用 FSCV 进行药理学操作和高效液相色谱法进行脑组织含量分析，来评估 DA 动力学的变化，以评估 DA D3 自身受体功能。
甲苯暴露的小鼠在重复暴露七天后，仅在伏隔核核心中观察到刺激的 DA 释放减少。仅在暴露于 2000 ppm 后，核心中的 DA 摄取减少。刺激的 DA 释放的差异与组织含量分析测量的神经元内 DA 水平的变化无关。空气和甲苯处理的小鼠之间的基础细胞外 DA 水平没有显着差异。然而，在额外的甲苯暴露后，在恢复期间，小鼠的伏隔核细胞外 DA 水平升高。这种细胞外伏隔核 DA 水平的增强在钾刺激下进一步加剧。DA D3 自身受体功能似乎没有作为这些差异的潜在介质发挥作用。
我们的 FSCV 和微透析结果表明，在伏隔核中 DA 释放机制发生了神经适应，但甲苯影响的确切神经元机制仍然难以捉摸。
