Modulation of Ethanol-Metabolizing Enzymes by Developmental Lead Exposure: Effects in Voluntary Ethanol Consumption

MIRIAM B. VIRGOLINI; MARA S. MATTALLONI; PAULA A. ALBRECHT; ROMINA DEZA-PONZIO ; LILIANA M. CANCELA

Frontiers in Behavioral Neuroscience

Frontiers in Behavioral Neuroscience

Año: 2017

1662-5153

Modulation of Ethanol-Metabolizing Enzymes by Developmental Lead Exposure: Effects in Voluntary Ethanol ConsumptionMiriam B. Virgolini* , Mara S. Mattalloni , Paula A. Albrecht , Romina Deza-Ponzioand Liliana M. CancelaIFEC-CONICET, Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba,Córdoba, ArgentinaThis review article provides evidence of the impact of the environmental contaminantlead (Pb) on the pattern of the motivational effects of ethanol (EtOH). To find amechanism that explains this interaction, the focus of this review article is on centralEtOH metabolism and the participating enzymes, as key factors in the modulation ofbrain acetaldehyde (ACD) accumulation and resulting effect on EtOH intake. Catalase(CAT) seems a good candidate for the shared mechanism between Pb and EtOH dueto both its antioxidant and its brain EtOH-metabolizing properties. CAT overactivationwas reported to increase EtOH consumption, while CAT blockade reduced it, and bothscenarios were modified by Pb exposure, probably as the result of elevated brain andblood CAT activity. Likewise, the motivational effects of EtOH were enhanced whenbrain ACD metabolism was prevented by ALDH2 inhibition, even in the Pb animalsthat evidenced reduced brain ALDH2 activity after chronic EtOH intake. Overall, theseresults suggest that brain EtOH metabolizing enzymes are modulated by Pb exposurewith resultant central ACD accumulation and a prevalence of the reinforcing effects of themetabolite in brain against the aversive peripheral ACD accumulation. They also supportthe idea that early exposure to an environmental contaminant, even at low doses,predisposes at a later age to differential reactivity to challenging events, increasing, inthis case, vulnerability to acquiring addictive behaviors, including excessive EtOH intake.