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

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.