Perinatal exposure to lead attenuates the conditioned reinforcing properties of cocaine in male rats.

The purpose of this study was to examine the effects of developmental lead exposure on drug responsiveness later in the life cycle. Adult female rats were gavaged daily with 0, 8, or 16 mg lead for 30 days before breeding with non-exposed males. The respective exposure regimens were maintained throughout gestation and lactation (perinatal exposure). In Experiment 1, at postnatal day (PND) 30 or 90, pups were trained with 0, 1.25, 2.5, or 5 mg/kg cocaine HCl (IP) in a biased conditioned place preference (CPP) procedure. At both PND 30 and 90, an attenuation in CPP was present in animals exposed to 8 or 16 mg lead relative to control rats. Using an identical lead-exposure regimen, a conditioned place aversion (CPA) procedure with 0, 10, 20, or 40 mg/kg lithium chloride (IP) was employed for Experiment 2. No significant differences were present among pups from each lead-exposure group conditioned and tested at PND 30 or 90, thus suggesting that an impairment of associative mechanisms was not solely responsible for the pattern of attenuation present in Experiment 1. Subsequent analyses of blood-lead in all experiments demonstrated concentrations below 5 microg/dl for all animals at PND 30 and below detectable limits (<1 microg/dl) at PND 90. The findings suggested attenuation in cocaine reinforcement with perinatal lead exposure even though the metal apparently had gained clearance from soft tissue.