Developmental exposure to environmentally-relevant concentrations of lead (Pb) elevates ethanol intake in Pb-exposed animals, with ethanol metabolism suggested to play a role. Acetaldehyde (ACD), ethanol first metabolite, has opposite effects in the organism: in addition to the well-known aversive consequences resulting of its accumulation in the periphery, centrally-formed ACD has positive reinforcing properties. In the present study, brain and liver ALDH (the enzyme that catalyzes ACD metabolism) was inhibited by cyanamide (CY) with the aim to evaluate the motivational and stimulant effects of ethanol. Thirty five-day old male 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 they were injected with CY, either systemically (25 mg/kg) or in the lateral brain ventricle (0.3 mg). Both, voluntary ethanol consumption and locomotor activity was measured. At the end of the test the animals were sacrificed and liver and brain dissected for ALDH activity assay. Systemic CY administration decreased both behaviors only in the Pb-exposed animals despite the finding that liver ALDH activity was equally inhibited in both groups. Oppositely, central CY administration inhibited brain ALDH activity and increased ethanol intake and locomotion selectively in the control rats, although a trend towards increased ethanol intake was evident in the Pb-exposed group. These results provide predictive value to the Pb-exposed model, and provide further evidence towards the importance of central ACD in ethanol?s motivational and stimulant effects.
Financial support: FonCyT, SeCyT and CONICET (MBV)
