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Background Environmental lead ( Pb) exposure and alcohol abuse pose significant public health problems for our society. One of the proposed mechanisms of action of the developmental neurotoxicant Pb is related to its ability to affect antioxidant enzymes, including catalase ( CAT). Ethanol's ( Et OH) motivational effects are postulated to be mediated by the CAT-dependent acetaldehyde generated in the brain. The current study sought to investigate the role of this enzyme in the elevated EtOH intake previously reported in perinatally Pb-exposed rats. Methods Thirty-five-day-old male Wistar rats exposed to 220 ppm Pb during gestation and lactation were offered escalating Et OH solutions (2 to 10%) or water, 2 h/d for 28 days. Once baseline 10% Et OH intake was achieved, they were injected with (i) saline ( SAL), (ii) 3-amino 1,2,4 triazole (aminotriazole [AT], a CAT inhibitor, 250 mg/kg intraperitoneally [i.p.], 5 hours before the last 8 Et OH intake sessions), or (iii) 3-nitropropionic acid (3 NPA; a CAT activator, 20 mg/kg subcutaneously [s.c.], 45 minutes before the last 4 Et OH intake sessions). Rats were then sacrificed, blood collected, and brain regions harvested for CAT activity determination. Additional studies evaluated Et OH intake and CAT activity in response to 10 and 30 mg/kg 3 NPA. Both 3 NPA and AT were evaluated for striatal cytotoxicity. Results We observed that AT pretreatment blunted the increased Et OH intake, as well as the elevated CAT activity in blood, cerebellum, and hippocampus evidenced in the developmentally Pb-exposed rats that have consumed Et OH. Conversely, 20 mg/kg 3 NPA further increased voluntary Et OH intake in these animals as compared with controls, concomitantly with a slight elevation in CAT activity both in blood and in the striatum, associated with no changes in striatal cytotoxicity. Conclusions These results suggest a participation of CAT, and possibly acetaldehyde, in Pb-induced high Et OH intake, and open up new avenues to elucidate the mechanism that underlies the Pb and Et OH interaction. [ABSTRACT FROM AUTHOR]