Early developmental lead exposure increases sensitivity to cocaine in a self-administration paradigm

The purpose of this investigation was to determine if lead exposure during pregnancy and nursing alters cocaine sensitivity later in the adult cycle, although lead exposure had been discontinued following early development. Female rats were exposed via gavage to 0 or 16 mg/kg lead daily for 30 days prior to breeding with nonexposed males. The respective daily exposure regimens continued throughout gestation and lactation (perinatal lead exposure). Lead exposure was discontinued on the day of weaning (postnatal day [PND] 21). Beginning on PND 70, male offspring were trained to self-administer cocaine HCl intravenously. Examination of a range of cocaine doses (0.030, 0.060, 0.125, 0.250, and 0.500 mg/kg/infusion) revealed that, as adults, animals exposed to lead during early development self-administered cocaine at significantly greater rates at a low dose of the drug. In addition, self-administration rates were lower among lead-exposed animals at higher doses of cocaine. These findings were observed in metal-exposed animals where blood and brain tissue levels had returned to the levels of controls. Collectively, these data suggest that early developmental lead exposure may increase sensitivity to cocaine later in the life cycle.