Developmental lead exposure alters the stimulatory properties of cocaine at PND 30 and PND 90 in the rat

The aim of this study was to examine the effects of perinatal lend exposure on locomotor responding following acute and repented cocaine challenges (s ensitization). Adult female rats were gavaged daily with 0, 8, or 16 mg len d acetate for 30 days prior to breeding. This exposure regimen was maintain ed throughout gestation and lactation (perinatal exposure). On Day 21, male pups were weaned and lend exposure was discontinued for the remainder of t he study. Beginning on postnatal day (PND) 30 or PND 90, and continuing for 14 successive days, separate groups of perinatally-exposed animals were pr esented with challenges of 10 mg/kg cocaine HCl (i.p.), and tested for loco motor responding. Following this testing period, dose-effect profiles were determined, with animals receiving daily injections of 0, 10, 20, and 40 mg /kg cocaine. The results indicated that both at PND 30 and PND 90 lead-expo sed animals were less responsive to the initial adiministration of cocaine, but exhibited a supersensitivity to the stimulatory effects associated wit h repented administration of cocaine, i.e., behavioral sensitization? to co caine was augmented by perinatal lend exposure. Analyses of blood lead leve ls following the completion of testing revealed that lead levels were below detectable limits for all animals (<1 mu g/dl). Collectively, these findin gs show that developmental lead contamination produces changes in cocaine s ensitivity long after exposure has been discontinued and the toxicant has g ained clearance blood. (C) 2000 American College of Neuropsychopharmacology . Published by Elsevier Science Inc.