Effects of acute and repeated exposures to Aroclor 1254 in adult rats: motor activity and flavor aversion conditioning.

Nobuyuki Nishida, Jackie D. Farmer, Prasad R. S. Kodavanti, Hugh A. Tilson, R. Macphail
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引用次数: 21

Abstract

While considerable research has focused on the neurotoxicity of developmental exposures to polychlorinated biphenyls, including Aroclor 1254, relatively little is known about exposures in adult animals. This study investigated the behavioral effects of acute and repeated Aroclor 1254 exposures to adult rats on motor activity and flavor aversion conditioning. Male Long-Evans rats (60 days old) were tested for motor activity in a photocell device after acute (0, 100, 300, or 1000 mg/kg, p.o.) or repeated (0, 1, 3, 10, 30 or 100 mg/kg/day, po, 5 days/week for 4 to 6 weeks exposure to Aroclor 1254. Motor activity was decreased dose-dependently at doses of 300 mg/kg or more after acute exposure. Severe body weight loss and deaths occurred at 1000 mg/kg. Recovery of activity occurred over 9 weeks but was incomplete. After repeated exposure, motor activity was decreased dose-dependently at doses of 30 mg/kg or more, and severe weight loss and deaths occurred at 100 mg/kg. In contrast to acute exposure, complete recovery of activity occurred 3 weeks after exposure. Additional rats were water deprived (30 min/day) and received acute po administration of Aroclor 1254 (0, 10, 15, 25, 30, 100, or 300 mg/kg) shortly after consuming a saccharin solution. Three days later they were given the choice between consuming saccharin or water, and saccharin preferences were recorded. Saccharin preference was decreased at doses of 25 mg/kg or more. Additional experiments determined the effect of repeated saccharin-Aroclor 1254 pairings (0, 3.75, 7.5, or 15 mg/kg/day, 14 days) followed by a choice test 1 day after the last dose. Repeated exposure to 15 mg/kg produced robust flavor aversion conditioning. Repeated exposure to 7.5 mg/kg produced flavor aversion conditioning in four of 12 rats. These results demonstrate that Aroclor 1254 causes hypoactivity and flavor aversions in adult rats; the no observable effect level (NOEL) for motor activity was 100 mg/kg for acute exposure and 10 mg/kg for repeated exposure for a period of up to 6 weeks. The acute NOEL for flavor aversion conditioning was 15 mg/kg while the repeated NOEL was 7.5 mg/kg.
急性和反复暴露于Aroclor 1254对成年大鼠的影响:运动活动和气味厌恶条件反射。
虽然相当多的研究集中在多氯联苯(包括Aroclor 1254)的发育暴露的神经毒性上,但对成年动物的暴露知之甚少。本研究探讨了急性和重复暴露于成年大鼠的Aroclor 1254对运动活动和气味厌恶条件反射的行为影响。在急性(0、100、300或1000 mg/kg,每天)或重复(0、1、3、10、30或100 mg/kg/天,每天,5天/周,连续4至6周暴露于Aroclor 1254后,在光电池装置中测试雄性龙-埃文思大鼠(60日龄)的运动活动。急性暴露后,300 mg/kg或更高剂量的运动活性呈剂量依赖性降低。1000 mg/kg时发生严重体重减轻和死亡。活动恢复超过9周,但不完全。重复暴露后,在剂量为30 mg/kg或更高时,运动活动呈剂量依赖性降低,在剂量为100 mg/kg时发生严重体重减轻和死亡。与急性暴露相比,暴露后3周活动完全恢复。另外的大鼠被剥夺水分(30分钟/天),并在摄入糖精溶液后不久接受Aroclor 1254(0、10、15、25、30、100或300 mg/kg)的急性静脉注射。三天后,研究人员让他们在摄入糖精和水之间做出选择,并记录下他们对糖精的偏好。在25 mg/kg或更高剂量时,糖精偏好降低。另外的实验确定了糖精- aroclor 1254重复配对(0、3.75、7.5或15 mg/kg/天,14天)的效果,并在最后一次给药后1天进行选择试验。重复暴露于15mg /kg产生强烈的风味厌恶条件。12只大鼠中的4只反复暴露于7.5 mg/kg的剂量下,产生了气味厌恶条件反射。这些结果表明,Aroclor 1254引起成年大鼠活动不足和气味厌恶;对运动活动的无观察效应水平(NOEL)为急性暴露为100 mg/kg,重复暴露为10 mg/kg,持续时间长达6周。厌味调节急性期NOEL为15 mg/kg,重复期NOEL为7.5 mg/kg。
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