Silencing brain catalase expression reduces ethanol intake in developmentally-lead-exposed rats

Abstract

Lead (Pb) is a developmental neurotoxicant. We have demonstrated that perinatally Pb-exposed rats consumemore ethanol than their control counterparts, a response that seems to be mediated by catalase (CAT) andcentrally-formed acetaldehyde, ethanol?s first metabolite with attributed reinforcing effects in the brain. Thepresent study sought to disrupt ethanol intake (2?10% ethanol v/v) in rats exposed to 220 ppm Pb or filteredwater during gestation and lactation. Thus, to block brain CAT expression, a lentiviral vector coding for a shRNAagainst CAT (LV-antiCAT vector) was microinfused in the posterior ventral tegmental area (pVTA) either at theonset or towards the end of a chronic voluntary ethanol consumption test. At the end of the study, rats wereeuthanized and pVTA dissected to measure CAT expression by Western blot. The LV-antiCAT vector administrationnot only reversed, but also prevented the emergence of the elevated ethanol intake reported in theperinatally Pb-exposed animals, changes that were supported by a significant reduction in CAT expression in thepVTA. These results provide further evidence of the crucial role of this enzyme in the reinforcing properties ofethanol and in the impact of the perinatal Pb programming to challenging events later in life.