Nation Jack R, Smith Kelly R, Bratton Gerald R
Department of Psychology, Texas A&M University, College Station, TX 77843, USA.
Pharmacol Biochem Behav. 2004 Jan;77(1):127-35. doi: 10.1016/j.pbb.2003.10.009.
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.
本研究的目的是确定孕期和哺乳期的铅暴露是否会改变成年期后期对可卡因的敏感性，尽管在早期发育后铅暴露已停止。在与未接触铅的雄性大鼠交配前30天，雌性大鼠通过灌胃每天接受0或16mg/kg的铅暴露。在整个妊娠期和哺乳期（围产期铅暴露）持续相应的每日暴露方案。在断奶日（出生后第21天）停止铅暴露。从出生后第70天开始，对雄性后代进行静脉注射盐酸可卡因的自我给药训练。对一系列可卡因剂量（0.030、0.060、0.125、0.250和0.500mg/kg/次注射）的检查显示，作为成年动物，早期发育期间接触铅的动物在低剂量药物时自我给药可卡因的速率明显更高。此外，在高剂量可卡因时，接触铅的动物的自我给药速率较低。在血液和脑组织水平已恢复到对照水平的金属暴露动物中观察到了这些发现。总体而言，这些数据表明，早期发育期间的铅暴露可能会增加生命周期后期对可卡因的敏感性。
