OPPOSITEETHANOL EFFECTS INDUCED BY CENTRAL vs. SYSTEMIC CYANAMIDE ADMINISTRATION IN DEVELOPMENTALLY-LEAD-EXPOSEDRATS

Mara S.Mattalloni, Romina Deza-Ponzio, Paula A. Albrecht, Liliana M. Cancela & MiriamB. Virgolini

IFEC-CONICET.Depto. de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional deCórdoba, Argentina

Developmental exposure toenvironmentally-relevant concentrations of lead (Pb) elevates ethanol intake inPb-exposed animals, with ethanol metabolism suggested to play a role.Acetaldehyde (ACD), ethanol first metabolite, has opposite effects in theorganism: in addition to the well-known aversive consequences resulting of itsaccumulation in the periphery, centrally-formed ACD has positive reinforcingproperties. In the present study, brain and liver ALDH (the enzyme thatcatalyzes ACD metabolism) was inhibited by cyanamide (CY) with the aim toevaluate the motivational and stimulant effects of ethanol. Thirty five-day oldmale Wistar rats perinatally exposed to 220 ppm Pb were offered with ethanol(2-10% v/v) or water during 28 days; on the last 4 days of the experiment theywere injected with CY, either systemically (25 mg/kg) or in the lateral brainventricle (0.3 mg). Both, voluntary ethanol consumption and locomotor activitywas measured. At the end of the test the animals were sacrificed and liver andbrain dissected for ALDH activity assay. Systemic CY administration decreasedboth behaviors only in the Pb-exposed animals despite the finding that liverALDH activity was equally inhibited in both groups. Oppositely, central CYadministration inhibited brain ALDH activity and increased ethanol intake andlocomotion selectively in the control rats, although a trend towards increasedethanol intake was evident in the Pb-exposed group. These results providepredictive value to the Pb-exposed model, and provide further evidence towardsthe importance of central ACD in ethanol?s motivational and stimulant effects.

Financial support: FonCyT, SeCyTand CONICET (MBV)