ALTERING ETOH METABOLISM: THE ROLE OF ACETALDEHYDE IN ETHANOL LOCOMOTIVE EFFECTS IN INFANT RATS

MARCH, S.M.; MOLINA, J.C.

CONCEPCION

Congreso; I LASBRA-LARNEDA Joint Meeting on Alcohol and other Drugs of Abuse: From molecules to human disorders; 2013

LATIN AMERICAN SOCIETY FOR BIOMEDICAL RESEARCH ON ALCOHOLISM

Central Acetaldehyde (ACD) accumulation has been linked to ethanol induced locomotion and reward. Opposite effects have been linked to peripheral accumulation of this metabolite. Interestingly, central effects derived from ethanol exposure varies across ontogeny. The catalase system, wich metabolizes EtOH into ACD in the brain, is more active during early life. Previously, we found that ACD is necessary for the acquisition of an appettitive conditioning in newborn rats. Here, we analyze the role of ACD in EtOH induced locomotion and sedation in infant rats. In Experiment 1, 15 day old rats received EtOH (i.g.: 0.0; 0.5; 1,5 and 2,5 g/kg) one hour after cianamide administration (0 or 10 mg). Five and 45 minutes later, locomotive activity was rated in an open field during 5 minutes. Results: EtOH significantly increased locomotive activity shortly after administration (min 5-10, doses 1.5 and 2.5 g/kg). During postadministration time 45-50, cianamide significantly decreased motor activity in pups administered with EtOH (0.5; 1.5; and 2.5 g/kg), compared to control siblings (group 0.0 g/kg EtOH). In Experiment 2, locomotive activity was assessed as a function of EtOH (0.0 and 2.5 g/kg), and cianamide or cianamide plus 4-metylpirazol (0 or 10 mg) administration. Whereas cianamide reduced motor activity in ethanol administered rats, 4-MP blocked this effect. Experiment 3 assessed EtOH blood levels using manipulations similar to those used in experiment 2. Cianamide administration significantly decreased circulating levels of EtOH, 4MP blocked this effect. Present results indicate that peripheral ACD accumulation decreased locomotion, but ETOH accumulation reverts this effect.