LEAD-INDUCED ETHANOL SELF-ADMINISTRATION IS DISRUPTED BY CATALASE MODULATORS: A ROLE FOR ACETALDEHYDE?
Mattalloni, M.S.; De Giovanni, L.N.; Cancela, L.M.; Virgolini, M.B.
IFEC-CONICET. Depto. de Farmacología. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. Córdoba. Argentina. marsol214@hotmail.com
Previous evidences indicate that perinatal low-level lead (Pb) exposure increases ethanol intake in a two-bottle ethanol/water paradigm. This effect was blunted by a catalase (CAT) inhibitor (aminotriazole -AT) and further increased by a CAT booster (3-nitropropionic acid -3NPA), indicating a participation of the ethanol-metabolizing enzyme CAT in the drug motivational effects. The present study was aimed to evaluate the role of CAT in an operant oral ethanol self-administration task. Thirty-five day-old male Wistar pups perinatally exposed to 220 ppm Pb were trained to associate the contingency of a lever press with 10% ethanol administration. To this end, a shaping, fading, and a fixed-ratio 1 (FR-1) followed by a FR-2 acquisition procedure was applied. At this point, when stable rates of responding and the differences between groups emerged, the animals were injected with saline (SAL), AT (250 mg/kg i.p., 5 h before the test) or 3-NPA (20 mg/kg s.c., 75 min before the test). The results demonstrated that Pb-exposed animals presented higher rates of response in order to obtain ethanol at a FR-2 schedule of behavior, effect that was further increased by prior 3-NPA administration, and slightly attenuated by AT pre-treatment. These results provide further evidence to the higher ethanol motivational properties in low-level Pb exposed rats as compared to controls. They are also indicative of the importance of CAT and provide some hints of the participation of acetaldehyde in an operant ethanol self-administration paradigm.
Grants: SECyT, MinCyT, CONICET
