|
AUTHORS (LAST NAME, FIRST NAME): Virgolini, Miriam1; Mattalloni, Mara S.1; Cancela, Liliana M.1 |
|
SPONSOR NAME: None |
|
INSTITUTIONS (ALL): 1. IFEC CONICET Depto. de Farmacologia. , Fac. de Ciencias Quimicas. Universidad Nacional de Cordoba, Cordoba, Argentina. |
|
ABSTRACT BODY: Lead (Pb) is a developmental neurotoxicant that modify several responses to drugs of abuse. We have demonstrated that low-level Pb-exposed rats showed increased ethanol (ET) consumption in a limited free-choice paradigm compared to their control counterparts. The current study sought to investigate the role of catalase (CAT) on ET intake, being CAT an enzyme implicated in both, brain ethanol metabolism, and Pb-induced anti-oxidant defense system. We postulate that concomitant exposure to Pb and ET would stimulate CAT activity leading to the higher ET intake observed in developmentally Pb-exposed animals. Thirty-five day old animals exposed to 220 ppm Pb during gestation and lactation were evaluated in their voluntary ethanol intake during 2 h for 28 days according to the following scheme: days 1-4: ET 2%; days 5-8: ET 4%; days 9-12: ET 6%; days 13-16: ET 8%; days 17-20: ET 10%. After stable 10% ET consumption was achieved, all rats were injected with: 1) vehicle (saline); 2) an inhibitor of CAT activity: AT, 3-amino 1,2,4 triazole (0.25 mg/kg i.p.) 5 h before the onset of the daily ET choice session (days 21-28), or 3) an activator of CAT activity: 3-NPA, 3 nitropropionic acid (10, 20, and 30 mg/kg s.c.) 90 min before the corresponding ET choice session (days 25-28). Immediately after the last free-choice session, all rats were sacrificed and several brain regions harvested to measure brain CAT activity. Blood was also collected to measure CAT activity, Pb, and ET levels. A 35-day-old and a 70-day-old group that have not consumed ethanol were included. We demonstrated that pretreatment with AT blunted, whereas 3NPA (20 mg/kg) further increased the higher voluntary ET intake previously observed in Pb-exposed rats. Corresponding changes were observed in blood and brain CAT activity. These results emphasize the importance of CAT as an antioxidant enzyme and a key component of brain ET metabolism, ascribing a critical role for acetaldehyde in Pb-induced ET reinforcing effects. |
