Ivens I A, Schmuck G, Machemer L
Preclinical Research, Bayer Corporation, Berkeley, California 94710, USA.
Toxicol Sci. 1998 Nov;46(1):101-11. doi: 10.1006/toxs.1998.2508.
A set of four learning and memory tests (Morris Maze I for reference memory, Morris Maze II for working memory, one-way active avoidance, and passive avoidance) were employed to address the questions whether parathion impaired cognitive functions after low, long-term exposure and could cause persistent changes in cognition. Motor activity and general behavior were investigated in a functional observational battery. Parathion was administered in rat food in low doses which caused no clinical symptoms and no or borderline brain acetylcholinesterase inhibition. Parathion doses of 0.5, 2, or 8 ppm in rat food produced the averaged uptake of 24, 100, or 400 microg/kg body weight per group per day in male rats and 36, 152, or 550 microg/kg per day in female rats in week 13. Learning tests were performed in weeks 1 to 4 and 10 to 14, as well as 30 to 34 weeks after the end of treatment, when the male and female rats were about 13 months old. Low doses of parathion given daily for 13 weeks had no cumulative or adverse effects on learning and memory, either during treatment or after the extended treatment-free period, in any of the tests. A significant improvement of learning compared to control observed in the Morris Water Maze I during the first week of treatment (males dose group 0.5 ppm) shows that parathion can improved cognitive functions in rats. Results of the study indicate that adverse effects changing learning and memory in animals may occur only at higher doses of organophosphates, at which the peripheral and brain acetylcholinesterases are inhibited to a greater extent than those in the present study.
采用一组四项学习和记忆测试(用于参考记忆的莫里斯迷宫I、用于工作记忆的莫里斯迷宫II、单向主动回避和被动回避)来解决以下问题:长期低剂量接触对硫磷是否会损害认知功能,以及是否会导致认知的持续变化。在功能性观察组合中研究运动活动和一般行为。对硫磷以低剂量添加到大鼠食物中,未引起临床症状,也未抑制或仅轻微抑制脑乙酰胆碱酯酶。在第13周时,大鼠食物中对硫磷剂量为0.5、2或8 ppm,雄性大鼠每组每天平均摄入量分别为24、100或400微克/千克体重,雌性大鼠分别为36、152或550微克/千克体重。学习测试在治疗结束后的第1至4周、10至14周以及30至34周进行,此时雄性和雌性大鼠约13个月大。在任何测试中,连续13周每天给予低剂量对硫磷,在治疗期间或延长的无治疗期后,对学习和记忆均无累积或不良影响。在治疗的第一周,在莫里斯水迷宫I中观察到与对照组相比,学习有显著改善(雄性大鼠剂量组0.5 ppm),这表明对硫磷可以改善大鼠的认知功能。研究结果表明,只有在较高剂量的有机磷化合物下,才可能对动物的学习和记忆产生不良影响,此时外周和脑乙酰胆碱酯酶的抑制程度比本研究中的更大。