Brockel B J, Cory-Slechta D A
Department of Environmental Medicine, University of Rochester Medical School, NY 14642, USA.
Pharmacol Biochem Behav. 1999 Jul;63(3):423-34. doi: 10.1016/s0091-3057(99)00033-7.
Some behavioral changes produced by chronic postweaning lead (Pb) exposure have been linked to mesolimbic dopamine (DA) system alterations. This study sought to determine the role of DA systems in Pb-induced changes in a fixed ratio (FR) waiting-for-reward paradigm. Rats exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions earned free reinforcers for waiting after completion of an FR, with increasing time between successive free reinforcers. Responses during the waiting period reset the FR requirement. Once performance stabilized, the effects of acute IP administration of the D1 agonist SKF82958, the D2 agonist quinpirole, the D1 antagonist SCH23390, and the D2 antagonist eticlopride were determined. Pb itself increased FR response rates and decreased mean waiting time, a pattern of behavior that increased the number of earned reinforcers, but doubled the number of responses/reinforcer. None of the DA compounds mimicked Pb effects when administered to controls. Only DA agonists altered waiting behavior and responses per reinforcer. Quinpirole, in particular, appeared to reverse Pb effects on the FR wait baseline by increasing waiting time and decreasing FR resets to control levels. These findings point to a particular role for D2 DA function in Pb's detrimental effects on waiting.
断奶后长期铅（Pb）暴露所产生的一些行为变化与中脑边缘多巴胺（DA）系统改变有关。本研究旨在确定DA系统在铅诱导的固定比率（FR）等待奖励范式变化中的作用。从断奶开始长期暴露于0、50或150 ppm醋酸铅饮用水溶液的大鼠，在完成一次FR后等待可获得免费强化物，连续免费强化物之间的时间间隔逐渐增加。等待期间的反应会重置FR要求。一旦表现稳定，就确定急性腹腔注射D1激动剂SKF82958、D2激动剂喹吡罗、D1拮抗剂SCH23390和D2拮抗剂依替必利的效果。铅本身会提高FR反应率并缩短平均等待时间，这种行为模式增加了获得强化物的数量，但使每次强化物的反应次数增加了一倍。给对照组注射时，没有一种DA化合物能模拟铅的作用。只有DA激动剂改变了等待行为和每次强化物的反应。特别是喹吡罗，似乎通过延长等待时间并将FR重置减少到对照水平来逆转铅对FR等待基线的影响。这些发现表明D2 DA功能在铅对等待的有害影响中具有特殊作用。
