IMPACT OF SYSTEMICCYANAMIDE ADMINISTRATION IN DEVELOPMENTALLY LOW-LEVEL LEAD-EXPOSED RATS:ETHANOL MOTIVATIONAL AND STIMULANT EFFECTS AND ENZYMATIC BIOMARKERS
Deza-Ponzio R, Mattalloni MS, Zar G, CancelaLM and Virgolini MB
IFEC.CONICET.Depto. de Farmacología. Facultad de Ciencias Químicas. Haya de la Torre yMedina Allende. Ciudad Universitaria. 5016. Córdoba,Argentina.
Wehave demonstrated that the developmental neurotoxicant lead (Pb) increasesethanol intake in a free-choice paradigm, which is associated with hyperlocomotionassessed immediately thereafter. Peripheral ethanol oxidation to acetaldehydeis exerted by ADH (alcohol dehydrogenase) -with catalase (CAT) playing a minorrole- while ALDH2 (aldehyde dehydrogenase 2) is involved in acetaldehydeoxidation to acetate. Cyanamide (CYAN), an ALDH2 inhibitor (which also producesslight CAT inhibition) is prescribed to treat alcoholism in several countries dueto peripheral toxic acetaldehyde accumulation. Thus, in the present study wesought to determine whether systemically-administered CYAN blunt the elevatedethanol intake and associated hyperlocomotion evidenced in Pb-exposed animals. Malethirty-five day-old rats exposed to Pb (220 ppm) or tap water (control group:C) through gestation and lactation were offered four bottles, two containingwater and the other two increasing ethanol concentrations (2% to 10%) in a 2-hfree-choice test. On test day 25, once 10% ethanol intake was stabilized and ahigher ethanol intake was evident in Pb-exposed animals, they were injectedwith saline (SAL) or CYAN (25 mg/kg i.p.) thirty minutes before the last fourethanol intake sessions. This was followed by a locomotor activity test and decapitationthereafter to collect blood, brain and liver tissue to determine CAT and ALDHactivities by spectrophotometric analysis. CAT activity was measured by the H2O2disappearance at 240 nm, while ALDH2 activity was determined by NADH formationat 340 nm. The behavioral data revealed that ethanol intake (mg/kg) wassignificantly reduced in the Pb-exposed animals as a consequence of CYANadministration: C-SAL: 0.70+0.09; C-CYAN: 0.70+0.14; Pb-SAL: 2.03+0.18;Pb-CYAN: 0.89+0.08. In the same line, ethanol-induced locomotor activitywas considerably abrogated in Pb-exposed rats. Preliminary results indicate theabsence of differences in brain and blood CAT activity; ALDH in brain seemed tobe reduced only in the cerebellum in both, control and Pb-exposed animals. Wepostulate that peripheral acetaldehyde accumulation produces aversive symptomsthat can account for the reduction in the excessive ethanol intake observed indevelopmental Pb-exposed rats, a finding that provides predictive validity toour model.
KEYWORDS:Lead exposure ? Alcohol ? Acetaldehyde - Cyanamide
