Wiaderna Dorota, Tomas Tadeusz
Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lódź, Poland.
Int J Occup Med Environ Health. 2002;15(3):239-45.
Toluene is a major component of numerous commercial organic solvent formulations. It is often listed among the chemicals capable of producing the organic solvent syndrome and a neurobehavioral hypersensitivity condition. The hypersensitivity condition (continued long-term intensification of some behavioral reactions in response to pharmacological or environmental stressors) is usually associated with the increased tonus of the functional dopaminergic system. The aim of our current research was to determine whether, under conditions of inhalation exposure, toluene can produce long-term behavioral changes or modify the intensity of the behavioral response to apomorphine, a dopaminergic receptor agonist. In our experiment, male rats were exposed to 25, 100 and 250 ppm toluene for 4 weeks (5 days/week, 6h/day). The following behaviors were tested: finding water in a radial maze; open field motor activity, acquiring the conditional response of passive avoidance; sensitivity to a thermal pain stimulus (hot plate test) and changes in this sensitivity caused by stress; and acquiring the conditional response of two-directional active avoidance. The behavioral response to apomorphine, i.e. the increased spontaneous locomotor activity, was assessed on day 10 after the termination of the exposure in the rotary drum test. In the behavioral experiment, significant differences between groups were recorded only for the hot plate test; in the 100 and 250 ppm rats, electric-shock-related anxiety response was stronger than in the control group. In the experiment using pharmacological provocation, the behavioral response to apomorphine in the rats exposed to 100 ppm or 250 ppm toluene was significantly lower. Our results indicate that low concentrations of toluene may produce long-term behavioral changes in rats. However, these changes seem to be linked with reduced rather than increased functional tonus of the dopaminergic system.
甲苯是众多商用有机溶剂配方中的主要成分。它常被列为能够引发有机溶剂综合征和一种神经行为超敏反应病症的化学物质。这种超敏反应病症(对药理学或环境应激源的某些行为反应持续长期增强)通常与功能性多巴胺能系统张力增加有关。我们当前研究的目的是确定在吸入暴露条件下,甲苯是否会产生长期行为变化,或者改变对多巴胺能受体激动剂阿扑吗啡的行为反应强度。在我们的实验中,雄性大鼠暴露于25、100和250 ppm的甲苯中4周(每周5天,每天6小时)。测试了以下行为:在放射状迷宫中找水;旷场运动活动、获得被动回避的条件反应;对热痛刺激(热板试验)的敏感性以及应激引起的这种敏感性变化;以及获得双向主动回避的条件反应。在暴露终止后的第10天,通过转鼓试验评估对阿扑吗啡的行为反应,即自发运动活动增加。在行为实验中,仅在热板试验中记录到组间存在显著差异;在100和250 ppm组的大鼠中,与电击相关的焦虑反应比对照组更强。在药理学激发实验中,暴露于100 ppm或250 ppm甲苯的大鼠对阿扑吗啡的行为反应显著降低。我们的结果表明,低浓度甲苯可能会在大鼠中产生长期行为变化。然而,这些变化似乎与多巴胺能系统功能张力降低而非增加有关。