title: Developmental lead exposure induces opposite effects on ethanol intake and locomotion in response to central vs. systemic cyanamide administration.
abstract: Lead (Pb) is a developmental neurotoxicant that elicits differential responses to drugs of abuse. Particularly, ethanol consumption has 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 with ethanol metabolism by inhibiting ALDH2 (mitochondrial aldehyde dehydrogenase) activity in both liver and brain from control and Pb-exposed rats as a strategy to accumulate ACD, a substance that plays a major role in the drug's reinforcing and/or aversive effects. To evaluate the impact on a 2-h chronic voluntary ethanol intake test, developmentally Pb-exposed and control rats were administered with cyanamide (CY, an ALDH inhibitor) either systemically or intracerebroventricularly (i.c.v.) on the last 4 sessions of the experiment. Furthermore, on the last session and after locomotor activity was assessed, all animals were 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 not in the controls) accompanied by liver (but not brain) ALDH2 inactivation. On the other hand, a 0.3 mg i.c.v. CY administration enhanced both ethanol intake and locomotor activity accompanied by brain ALDH2 inactivation in control animals, while an increase in ethanol consumption was also observed in the Pb-exposed group, although in the absence of 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 that are modulated by developmental Pb exposure.
authors.affiliation: IFEC - CONICET, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5016, Córdoba, Argentina; Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5016, Córdoba, Argentina.
authors.forename: Mara Soledad
authors.initials: MS
authors.lastname: Mattalloni
authors.affiliation: IFEC - CONICET, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5016, Córdoba, Argentina; Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5016, Córdoba, Argentina.
authors.forename: Romina
authors.initials: R
authors.lastname: Deza-Ponzio
authors.affiliation: IFEC - CONICET, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5016, Córdoba, Argentina; Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5016, Córdoba, Argentina.
authors.forename: Paula Alejandra
authors.initials: PA
authors.lastname: Albrecht
authors.affiliation: IFEC - CONICET, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5016, Córdoba, Argentina; Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5016, Córdoba, Argentina.
authors.forename: Liliana Marina
authors.initials: LM
authors.lastname: Cancela
authors.affiliation: IFEC - CONICET, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5016, Córdoba, Argentina; Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5016, Córdoba, Argentina. Electronic address: mvirgoli@fcq.unc.edu.ar.
authors.forename: Miriam Beatriz
authors.initials: MB
authors.lastname: Virgolini
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism / Q000523:psychology*; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*; D003484:Cyanamide / Q000008:administration & dosage*; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007276:Injections, Intraventricular; D007854:Lead / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007854:Lead; D000431:Ethanol; D003484:Cyanamide; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat
keywords: ALDH2; Acetaldehyde; Catalase; Ethanol intake and locomotion; Lead exposure