Lead (Pb) is a developmental neurotoxicant. We have demonstrated that perinatally Pb-exposed rats consume more ethanol than their control counterparts, a response that seems to be mediated by catalase (CAT) and centrally-formed acetaldehyde, ethanol’s first metabolite with attributed reinforcing effects in the brain. The present study sought to disrupt ethanol intake (2–10% ethanol v/v) in rats exposed to 220 ppm Pb or filtered water during gestation and lactation. Thus, to block brain CAT expression, a lentiviral vector coding for a shRNA against CAT (LV-antiCAT vector) was microinfused in the posterior ventral tegmental area (pVTA) either at the onset or towards the end of a chronic voluntary ethanol consumption test. At the end of the study, rats were euthanized and pVTA dissected to measure CAT expression by Western blot. The LV-antiCAT vector administration not only reversed, but also prevented the emergence of the elevated ethanol intake reported in the perinatally Pb-exposed animals, changes that were supported by a significant reduction in CAT expression in the pVTA. These results provide further evidence of the crucial role of this enzyme in the reinforcing properties of ethanol and in the impact of the perinatal Pb programming to challenging events later in life.

铅（Pb）是一种发育性神经毒剂。我们已经证明，围生期暴露于Pb的大鼠比对照大鼠消耗更多的乙醇，这种反应似乎由过氧化氢酶（CAT）和集中形成的乙醛介导，乙醛是乙醇的第一种代谢产物，在大脑中具有增强作用。本研究试图破坏妊娠和哺乳期暴露于220 ppm Pb或过滤水的大鼠的乙醇摄入量（2-10％乙醇v / v）。因此，为了阻断脑CAT的表达，在慢性自愿性酒精消耗试验的开始或结束时，将编码针对CAT的shRNA的慢病毒载体（LV-antiCAT载体）微注入后腹盖区（pVTA）。在研究结束时，对大鼠实施安乐死并解剖pVTA，以通过Western blot检测CAT的表达。LV-antiCAT载体的施用不仅可以逆转，而且可以防止围产期Pb暴露的动物中乙醇摄入量的增加，这种变化得到了pVTA中CAT表达的显着降低的支持。这些结果进一步证明了该酶在乙醇的增强特性以及围产期铅编程对生活中挑战性事件的影响中的关键作用。