BLOCKADE OF BRAIN ETHANOL METABOLISM BY CENTRALLY-ADMINISTERED CYANAMIDE: EFFECTS ON ETHANOL INTAKE, LOCOMOTOR ACTIVITY AND PARTICIPATING ENZYMES IN A PERINATAL LEAD EXPOSURE MODEL
Mattalloni MS, Deza-Ponzio R, Albrecht PA, Cancela LM and Virgolini MB
IFEC-CONICET. Depto. de Farmacología. Facultad de Ciencias Químicas. Haya de la Torre y Medina Allende. Ciudad Universitaria. 5016. Córdoba, Argentina.
In pursuing the putative mechanism for the increased vulnerability to consume ethanol reported in developmentally-lead (Pb)-exposed rats, we have demonstrated that catalase activity (CAT, the main enzyme involved in brain ethanol metabolism) is elevated in the blood and brain of these animals. Moreover, we have also reported that the ethanol ingested in the free-choice test is sufficient for the Pb-exposed animals to evidence hyperactivity. We thus postulate that brain ethanol-derived acetaldehyde could be in part responsible of the increased motivational and stimulant properties of ethanol in Pb-exposed rats. To this end, cyanamide, an ALDH2 blocker (being ALDH2 the enzyme responsive for acetaldehyde degradation) was administered in the lateral ventricle to interfere with acetaldehyde metabolism in the brain. Male thirty-five day-old animals were subjected to a 2-h free-choice test (2 bottles filled with water and 2 bottles filled with ethanol solutions at 2-10%). Once 10% ethanol intake was stabilized and Pb animals evidenced elevated ethanol intake in comparison to controls, they were microinfused with vehicle, 0.1, 0.2 or 0.3 µg cyanamide immediately before the free-choice session; and their ethanol-induced hyperlocomotion assessed immediately thereafter. At the end of the one-hour locomotor activity session they were sacrificed to determine brain CAT and ALDH2 activity. The results demonstrate that cyanamide increase ethanol intake and locomotor activity in control animals at all the three doses evaluated whereas, only the two higher doses we able to increase the same behaviors in the Pb-exposed group. In relation to brain CAT activity, a reduction was observed only in the control group at the higher dose evaluated. However, we failed to evidence a significant reduction in brain ALDH2 activity. These results support the importance of brain ethanol-derived acetaldehyde as a putative metabolite implicated in the motivational and stimulant effects of ethanol.
