Congresos y reuniones científicas
Título:
Blockade of brain ethanol metabolism by centrally-administered cyanamide: effects on ethanol intake, locomotor activity and participating enzymes in a perinatal lead exposure model
Autor/es:
MATTALLONI MS ; DEZA-PONZIO R; ALBRECHT PA; CANCELA LM; VIRGOLINI MB
Reunión:
Congreso; 3° Reunión Internacional de Ciencias Farmacéuticas; 2014
Institución organizadora:
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba y Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario
Resumen:
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 Pbexposed
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 Pbexposed
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 were 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.