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

MARA S. MATTALLONI; DEZA-PONZIO, ROMINA; ALBRECHT, PAULA A.; LUCIA E. FERNANDEZ-HUBEID; CANCELA LILIANA MARINA; MIRIAM B. VIRGOLINI

NEUROTOXICOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2019

0161-813X

Developmentally-lead (Pb)-exposed rats showed an enhancedvulnerability to the stimulating and motivational effects of ethanol(EtOH). This is accompanied by differential activity of the brain EtOHmetabolizing enzymes catalase (CAT) and mitochondrial aldehydedehydrogenase (ALDH2). Based on the theory that brain acetaldehydeaccumulation is associated to the reinforcing properties of EtOH, thisstudy sought to determine brain CAT and ALDH2 expression in limbic areasof control and Pb-exposed animals after voluntary EtOH intake. Thirtyfive-day-old perinatally Pb-exposed animals (220 ppm Pb) were offeredwith water or increasing EtOH solutions (2-10%) during 28 days untilpostnatal day (PND) 63. Once intake was stable, the animals wereadministered with: 1) vehicle (VEH; test days 21-24 or 21-28, ascorresponds), or 2) a CAT activity inhibitor: 3-amine 1, 2, 4-triazole(AT; 250 mg/kg intraperitoneally [i.p.], 5 hours before the last eightEtOH intake sessions -test days 21-24 and 25-28), or 3) a CAT activitybooster: 3-nitropropionic acid (3NPA; 20 mg/kg subcutaneously [s.c.], 45minutes before the last four EtOH intake sessions -test days 25-28), or4) cyanamide (CY, an ALDH2 inhibitor, 0.3 mg i.c.v. immediately beforethe last four EtOH sessions, test days 25-28). Lead exposure increasedEtOH intake, an effect potentiated in both groups by 3NPA or CYpretreatments and reduced by AT, albeit selectivity in the Pb group.Catalase abundance in limbic areas parallels these observations in the Pbgroup, showing higher than the controls CAT expression in all areas afterEtOH consumption, an effect prevented by AT administration. In contrast,ALDH2 expression was reduced in the Pb animals after EtOH intake, with CYfurther reducing this effect in all brain areas under study. Based onthese results and on previous evidences, we suggest that Pb exposurepromotes acetaldehyde accumulation in limbic regions, providing someinsights into the mechanism of action that underlies the vulnerability toexcessive EtOH consumption reported in these animals.