Brain ethanol-metabolizing enzymes are differentially expressed in lead-exposed animals after voluntary ethanol consumption: Pharmacological approaches.

MATTALLONI MS.; DEZA-PONZIO R; ALBRECHT PA; FERNANDEZ HUBEID, LE; CANCELA, L.M.; VIRGOLINI MB

NEUROTOXICOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2019

0161-813X

Developmentally-lead (Pb)-exposed rats showed an enhanced vulnerability to the stimulating and motivationaleffects of ethanol (EtOH). This is accompanied by differential activity of the brain EtOH-metabolizing enzymescatalase (CAT) and mitochondrial aldehyde dehydrogenase (ALDH2). Based on the theory that brain acetaldehydeaccumulation is associated with the reinforcing properties of EtOH, this study sought to determine brainCAT and ALDH2 expression in limbic areas of control and Pb-exposed animals after voluntary EtOH intake.Thirty-five-day-old rats perinatally exposed to 220ppm Pb were offered with water or increasing EtOH solutions(2?10% v/v) during 28 days until postnatal day (PND) 63. Once intake was stable, the animals were administered:1) saline (SAL; test days 21?24 or 21?28, as corresponds), or 2) a CAT inhibitor: 3-amine 1, 2, 4-triazole(AT; 250mg/kg intraperitoneally [i.p.], 5h before the last eight EtOH intake sessions -test days 21?24 and25?28), or 3) a CAT booster: 3-nitropropionic acid (3NPA; 20mg/kg subcutaneously [s.c.], 45min before the lastfour EtOH intake sessions -test days 25?28). Two additional groups were centrally-administered cyanamide (CY,an ALDH2 inhibitor, 0.3mg i.c.v. immediately before the last four EtOH sessions, test days 25?28) or its correspondingvehicle (VEH). Lead exposure increased EtOH intake, an effect potentiated in both groups by 3NPA orCY pretreatments and reduced by AT, albeit selectivity in the Pb group. Catalase abundance in limbic areas parallelsthese observations in the Pb group, showing higher CAT expression in all areas after EtOH consumptionrespect to the controls, an effect prevented by AT administration. In contrast, ALDH2 expression was reduced inthe Pb animals after EtOH intake, with CY potentiating this effect in all brain areas under study. Based on theseresults and on previous evidences, we suggest that Pb exposure promotes acetaldehyde accumulation in limbicregions, providing some insights into the mechanism of action that underlies the vulnerability to the excessiveEtOH consumption reported in these animals.