BLOCKADE OF BRAINETHANOL METABOLISM BY CENTRALLY-ADMINISTERED CYANAMIDE: EFFECTS ON ETHANOLINTAKE, LOCOMOTOR ACTIVITY AND PARTICIPATING ENZYMES IN A PERINATAL LEAD EXPOSUREMODEL
MattalloniMS, Deza-Ponzio R, Albrecht PA, Cancela LMand Virgolini MB
IFEC-CONICET. Depto. de Farmacología. Facultad de Ciencias Químicas.Haya de la Torre y Medina Allende. Ciudad Universitaria. 5016. Córdoba, Argentina.
Inpursuing the putative mechanism for the increased vulnerability to consumeethanol reported in developmentally-lead (Pb)-exposed rats, we havedemonstrated that catalase activity (CAT, the main enzyme involved in brainethanol metabolism) is elevated in the blood and brain of these animals.Moreover, we have also reported that the ethanol ingested in the free-choicetest is sufficient for the Pb-exposed animals to evidence hyperactivity. Wethus postulate that brain ethanol-derived acetaldehyde could be in partresponsible of the increased motivational and stimulant properties of ethanolin Pb-exposed rats. To this end, cyanamide, an ALDH2 blocker (being ALDH2 theenzyme responsive for acetaldehyde degradation) was administered in the lateralventricle to interfere with acetaldehyde metabolism in the brain. Malethirty-five day-old animals were subjected to a 2-h free-choice test (2 bottlesfilled with water and 2 bottles filled with ethanol solutions at 2-10%). Once10% ethanol intake was stabilized and Pb animals evidenced elevated ethanolintake in comparison to controls, they were microinfused with vehicle, 0.1, 0.2or 0.3 µg cyanamide immediately before the free-choice session; and theirethanol-induced hyperlocomotion assessed immediately thereafter. At the end ofthe one-hour locomotor activity session they were sacrificed to determine brainCAT and ALDH2 activity. The results demonstrate that cyanamide increase ethanolintake and locomotor activity in control animals at all the three dosesevaluated whereas, only the two higher doses we able to increase the samebehaviors in the Pb-exposed group. In relation to brain CAT activity, areduction 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 aputative metabolite implicated in the motivational and stimulant effects of ethanol.
LEADEXPOSURE, ETHANOL, ACETALDEHYDE, CATALASE, ALDH
