CONICET | Buscador de Institutos y Recursos Humanos

Lead (Pb) is a developmental neurotoxicant that elicits differential responses to drugs of abuse. Particularly, ethanol consumptionhas been demonstrated to be increased as a consequence of environmental Pb exposure, with catalase (CAT)and brain acetaldehyde (ACD, the first metabolite of ethanol) playing a role. The present study sought to interfere withethanol metabolism by inhibiting ALDH2 (mitochondrial aldehyde dehydrogenase) activity in both liver and brain controland Pb-exposed rats as a strategy to accumulate ACD, a substance that plays a major role in the drug´s reinforcingand/or aversive effects.To evaluate the impact on a 2-h chronic voluntary ethanol intake test, developmentally Pb-exposed and control ratswere administered with cyanamide (CY, an ALDH inhibitor) either systemically or intracerebroventricularly (i.c.v.) onthe last 4 sessions of the experiment. Furthermore, on the last session and after locomotor activity was assessed, all animalswere sacrificed to obtain brain and liver samples for ALDH2 and CAT activity determination.Systemic CY administration reduced the elevated ethanol intake already reported in the Pb-exposed animals (but notin the controls) accompanied by liver (but not brain) ALDH2 inactivation. On the other hand, a 0.3 mg i.c.v. CY administrationenhanced both ethanol intake and locomotor activity accompanied by brain ALDH2 inactivation in controlanimals, while an increase in ethanol consumption was also observed in the Pb-exposed group, although in the absenceof brain ALDH2 blockade. No changes were observed in CAT activity as a consequence of CY administration.These results support the participation of liver and brain ACD in ethanol intake and locomotor activity, responses thatare modulated by developmental Pb exposure

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