ACTIVATION OF CATALASE BY 3-NITROPROPIONIC ACID INCREASES VOLUNTARY ETHANOL INTAKE IN CONTROL RATS AS COMPARED TO PERINATALLY Pb-EXPOSED ANIMALS
Mara S. Mattalloni, Liliana M. Cancela and Miriam B. Virgolini
IFEC-CONICET. Depto de Farmacologia. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. Córdoba. Argentina
Keywords: catalase- lead exposure- ethanol- 3-nitropropionic acid- 3-amino 1,2,4 triazole
Catalase (CAT) is an antioxidant enzyme with a key role in brain ethanol (ET) metabolism. We have demonstrated that the chronic administration of a CAT inhibitor, 3-amino 1,2,4 triazole (AT) prevents the manifestation of the increased voluntary ET intake and blunted the elevated CAT activity in blood and several brain regions from Pb-exposed animals. In the present study we sought to determinate the effects of the over activation of CAT on ET intake in both, control and Pb-exposed rats. Thirty-five day-old male Wistar rats exposed to 220 ppm Pb during gestation and lactation were submitted to voluntary ET intake during 2 h/day for 28 days. Once stable 10% ET intake was achieved, a subset of animals was injected with vehicle (SAL) or 30 mg/kg of 3-nitropropionic acid (3-NPA), a neurotoxin that boosts CAT activity (days 25-28; groups: 63d-ET-SAL and 63d-ET-chronic3NPA, respectively) while another subset of animals was injected with a single dose of 3-NPA (day 28; group 63d-ET-acute3NPA). All rats were sacrificed on day 28 immediately after the last free-choice ET session, and brain regions harvested to measure brain CAT activity. Blood was collected to analyze CAT activity, Pb, and ET levels. The results demonstrated that chronic (but not acute) 3-NPA administration increased voluntary ET intake in control animals to levels comparable to those of the Pb-exposed group injected with SAL or 3-NPA. The failure of the CAT activator to further increase ET intake in the Pb-exposed rats may be due to a ceiling effect or to 3-NPA neurotoxic effects on striatal neurons. The increases in blood CAT activity in response to 3-NPA were similar in both groups while the NAc was the only brain region from the Pb-exposed group that did not show an increase in brain CAT activity in response to chronic 3-NPA administration. These results are discussed in terms of the putative role of CAT in the increased voluntary ET intake observed in Pb-exposed rats.
Sources: SeCyT- CONICET- FONCyT
