Oshiro Wendy M, Krantz Q Todd, Bushnell Philip J
Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Neurotoxicol Teratol. 2007 Mar-Apr;29(2):247-54. doi: 10.1016/j.ntt.2006.11.001. Epub 2006 Nov 10.
Previous work showed that trichloroethylene (TCE) impairs sustained attention as evidenced by a reduction in accuracy and elevation of response latencies in rats trained to perform a visual signal detection task (SDT). This work also showed that these effects abate during repeated exposures if rats inhale TCE while performing the SDT. The present experiment sought to determine whether toluene, another commonly-used solvent, would induce tolerance similarly if inhaled repeatedly during SDT testing. Sixteen male, Long-Evans rats were trained to perform the SDT. Upon completion of training, rats were divided into 2 groups. In Phase I, concentration-effect functions were determined for toluene (0, 1200, 1600, 2000, 2400 ppm) in both groups. Toluene reduced the proportion of correct responses [P(correct)], and increased response time (RT) and response failures. In Phase II, Group-Tol inhaled 1600 ppm toluene while Group-Air inhaled clean air during 11 daily SDT sessions. In Group-Tol the effect of toluene on P(correct) abated after 3 days, while RT remained elevated for the duration of the repeated exposures. In Phase III, toluene concentration-effect functions were re-determined for both groups. Group-Air remained impaired on all test measures, whereas for Group-Tol, toluene did not reduce P(correct), but continued to increase RT. These data confirm our previous hypothesis that animals can develop tolerance to chemical exposures that impair appetitively-motivated behaviors if that impairment leads to loss of reinforcement.
先前的研究表明,三氯乙烯(TCE)会损害持续注意力,这在经过视觉信号检测任务(SDT)训练的大鼠中表现为准确性降低和反应潜伏期延长。这项研究还表明,如果大鼠在执行SDT任务时吸入TCE,那么在反复接触过程中这些影响会减弱。本实验旨在确定另一种常用溶剂甲苯在SDT测试期间反复吸入时是否会类似地诱导耐受性。16只雄性Long-Evans大鼠接受了SDT训练。训练完成后,大鼠被分为两组。在第一阶段,确定两组大鼠对甲苯(0、1200、1600、2000、2400 ppm)的浓度-效应函数。甲苯降低了正确反应的比例[P(正确)],并增加了反应时间(RT)和反应失误。在第二阶段,在11天的每日SDT测试期间,甲苯组吸入1600 ppm甲苯,而空气组吸入清洁空气。在甲苯组中,甲苯对P(正确)的影响在3天后减弱,而在反复接触期间RT仍然升高。在第三阶段,重新确定两组大鼠的甲苯浓度-效应函数。空气组在所有测试指标上仍然受损,而对于甲苯组,甲苯没有降低P(正确)的值,但继续增加RT。这些数据证实了我们先前的假设,即如果化学暴露导致强化物丧失从而损害了具有食欲动机的行为,动物可以对这种化学暴露产生耐受性。