Developmental lead exposure induces opposite effects on ethanol intake and locomotion in response to central vs. Systemic cyanamide administration

ALBRECHT, P.A; VIRGOLINI, M.B; DEZA-PONZIO, R; VIRGOLINI, M.B; DEZA-PONZIO, R; CANCELA, L.M; MATTALLONI, M.S; CANCELA, L.M; MATTALLONI, M.S; ALBRECHT, P.A

ALCOHOL

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2017 p. 1 - 11

0741-8329

Developmental lead exposure induces opposite effects on ethanolintake and locomotion in response to central vs. systemic cyanamideadministrationMara Soledad Mattalloni a, b, Romina Deza-Ponzio a, b, Paula Alejandra Albrecht a, b,Liliana Marina Cancela a, b, Miriam Beatriz Virgolini a, b, *a IFEC - CONICET, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5016, Cordoba, Argentinab Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Cordoba, Haya de la Torre y Medina Allende, CiudadUniversitaria, 5016, Cordoba, ArgentinaLead (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 environmentalPb exposure, with catalase (CAT) and brain acetaldehyde (ACD, the first metabolite of ethanol) playing arole. The present study sought to interfere with ethanol metabolism by inhibiting ALDH2 (mitochondrialaldehyde dehydrogenase) activity in both liver and brain from control and Pb-exposed rats as a strategyto 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-exposedand control rats were administered with cyanamide (CY, an ALDH inhibitor) either systemically orintracerebroventricularly (i.c.v.) on the last 4 sessions of the experiment. Furthermore, on the last sessionand after locomotor activity was assessed, all animals were sacrificed to obtain brain and liver samplesfor ALDH2 and CAT activity determination.Systemic CY administration reduced the elevated ethanol intake already reported in the Pb-exposedanimals (but not in the controls) accompanied by liver (but not brain) ALDH2 inactivation. On theother hand, a 0.3 mg i.c.v. CY administration enhanced both ethanol intake and locomotor activityaccompanied by brain ALDH2 inactivation in control animals, while an increase in ethanol consumptionwas also observed in the Pb-exposed group, although in the absence of brain ALDH2 blockade. Nochanges 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