Perinatal lead exposure sensitizes rats to the rewarding effects of cocaine, but not cocaine/3,4-methylenedioxymethamphetamine(MDMA) combinations

Abstract

Early-age lead exposure has been shown to have various behavioral effects later in life, including learning deficits and mental retardation. Recent evidence indicates that early lead exposure may serve as a risk factor for drug abuse later in life by increasing the reward potency of cocaine and other drugs of abuse. In an attempt to extend these findings, the current study looked at early lead exposure as a risk factor for later self-administration of cocaine and cocaine/3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). Female Sprague-Dawley rats were exposed daily to either 0 mg (n=6) or 16 mg (n=7) lead acetate via gavage. After 30 days of initial exposure, dams were bred with unexposed males. The exposure regimen continued throughout breeding, gestation, and lactation up to post-natal day (PND) 21. On PND 60, male pups from control (n=6) and lead-exposed (n=7) dams were implanted with a jugular catheter under surgical anesthesia. Subjects were trained to lever-press for .500 mg/kg/inf. cocaine. Following shaping, operant responding rates were examined for four doses of cocaine (.030, .060, .125, and .250 mg/kg/inf.) and cocaine/MDMA combinations (cocaine doses combined with .1 mg/kg/inf. MDMA). Analysis of results revealed that animals exposed to lead responded at higher rates for all doses of cocaine, with significant differences at low doses (.030 and .060 mg/kg/inf.). MDMA universally and dose-dependently suppressed responding for cocaine (significantly at .060 and .125 mg/kg/inf.). Early lead exposure had no effect on responding for the drug combination. The results imply that early lead exposure serves as a risk factor for later drug abuse by increasing the reward potency of cocaine and increasing sensitivity to the effects of cocaine/MDMA combinations. Further research to more fully characterize the relationship between environmental lead exposure and drug abuse and to determine the underlying mechanisms responsible for the observed behavioral effects may prove vital to our understanding of risk factors involved the selection and intake of commonly abused drugs.