IMPACT OF SYSTEMIC CYANAMIDE ADMINISTRATION IN DEVELOPMENTALLY LOW-LEVEL LEAD-EXPOSED RATS: ETHANOL MOTIVATIONAL AND STIMULANT EFFECTS AND ENZYMATIC BIOMARKERS
Deza-Ponzio R, Mattalloni MS, Zar G, Cancela LM and Virgolini MB
IFEC.CONICET. Depto. de Farmacología. Facultad de Ciencias Químicas. Haya de la Torre y Medina Allende. Ciudad Universitaria. 5016. Córdoba, Argentina.
We have demonstrated that the developmental neurotoxicant lead (Pb) increases ethanol intake in a free-choice paradigm, which is associated with hyperlocomotion assessed immediately thereafter. Peripheral ethanol oxidation to acetaldehyde is exerted by ADH (alcohol dehydrogenase) -with catalase (CAT) playing a minor role- while ALDH2 (aldehyde dehydrogenase 2) is involved in acetaldehyde oxidation to acetate. Cyanamide (CYAN), an ALDH2 inhibitor (which also produces slight CAT inhibition) is prescribed to treat alcoholism in several countries due to peripheral toxic acetaldehyde accumulation. Thus, in the present study we sought to determine whether systemically-administered CYAN blunt the elevated ethanol intake and associated hyperlocomotion evidenced in Pb-exposed animals. Male thirty-five day-old rats exposed to Pb (220 ppm) or tap water (control group: C) through gestation and lactation were offered four bottles, two containing water and the other two increasing ethanol concentrations (2% to 10%) in a 2-h free-choice test. On test day 25, once 10% ethanol intake was stabilized and a higher ethanol intake was evident in Pb-exposed animals, they were injected with saline (SAL) or CYAN (25 mg/kg i.p.) thirty minutes before the last four ethanol intake sessions. This was followed by a locomotor activity test and decapitation thereafter to collect blood, brain and liver tissue to determine CAT and ALDH activities by spectrophotometric analysis. CAT activity was measured by the H2O2 disappearance at 240 nm, while ALDH2 activity was determined by NADH formation at 340 nm. The behavioral data revealed that ethanol intake (mg/kg) was significantly reduced in the Pb-exposed animals as a consequence of CYAN administration: 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 activity was considerably abrogated in Pb-exposed rats. Preliminary results indicate the absence of differences in brain and blood CAT activity; ALDH in brain seemed to be reduced only in the cerebellum in both, control and Pb-exposed animals. We postulate that peripheral acetaldehyde accumulation produces aversive symptoms that can account for the reduction in the excessive ethanol intake observed in developmental Pb-exposed rats, a finding that provides predictive validity to our model.
KEYWORDS: Lead exposure ? Alcohol ? Acetaldehyde - Cyanamide
