HEAVY METALS AND POLYDRUG SELF-ADMINISTRATION

重金属和多种药物的自我给药

• 批准号: 6634297
• 负责人: JACK R NATION
• 金额: $ 26.25万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6634297
• 关键词: behavior test; behavioral /social science research tag; bioaccumulation; cadmium; cocaine; drug interactions; embryo /fetus drug adverse effect; embryo /fetus toxicology; environmental exposure; ethanol; heavy metals; heroin; laboratory rat; lead; mature animal; neurotoxicology; perinatal; self medication; statistics /biometry; substance abuse epidemiology; tissue /cell preparation

DESCRIPTION: (ADAPTED FROM APPLICANT'S ABSTRACT) Regarding metal/drug interaction experiments, previous self-administration reports have been limited to the effects of adult lead or cadmium exposure on ethanol or cocaine intake. To date, there have been no studies on the effects of developmental metal exposure on the patterns of drug selection and intake later in the adult cycle. Relevant to this issue, this laboratory has observed that responsiveness to cocaine and other dopamine agonists is altered by perinatal exposure to lead or cadmium, and these disturbances persist well into the adult cycle long after toxicants have gained clearance from soft tissue. Such seemingly permanent and potentially nonreversible effects are of potential importance with respect to predicting use patterns of drugs that impact dopamine and related systems. Accordingly, this project aims to investigate the effects of prenatal, postnatal, and perinatal exposure to lead or cadmium on the self-administration of cocaine, heroin, and combinations of heroin and cocaine. Dams will be exposed to 0, 8, or 16 mg lead (Exp. 1-3) or 0, 2.5, or 5 mg cadmium (Exp. 4-6), and cross-fostered pups will be tested as adults for the intravascular (iv) self-administration of cocaine, heroin, or cocaine/heroin combinations (speedball). Exp. 7-9 will determine the effects of prenatal, postnatal, and perinatal cadmium exposure on regional accumulation of cadmium in brain, as well as in blood, liver, kidney, and bone (tibia). Because lead exists in such high concentrations in the inner cities where drug abuse is more common, and because over 20 percent of pregnant women in the United States smoke tobacco that contains cadmium which is readily distributed to the fetus/neonate, results of the proposed project should enhance our understanding of possible linkages between environmental contamination during early development and drug selection and use later in life.

描述：（改编自申请人的摘要）关于金属/药物 交互实验，之前的自我管理报告受到限制 成人铅或镉暴露对乙醇或可卡因摄入量的影响。 迄今为止，还没有关于发育金属的影响的研究。 暴露于成人周期后期的药物选择和摄入模式。 与这个问题相关，本实验室观察到，对 可卡因和其他多巴胺激动剂会因围产期接触铅或 镉，这些干扰在成年后很长一段时间内持续存在 有毒物质已从软组织中清除。这种看似永久且 潜在的不可逆效应对于以下方面具有潜在的重要性 预测影响多巴胺和相关系统的药物的使用模式。 因此，该项目旨在调查产前、 自我给药导致产后和围产期接触铅或镉 可卡因、海洛因以及海洛因和可卡因的混合物。水坝将会 暴露于 0、8 或 16 mg 铅（实验 1-3）或 0、2.5 或 5 mg 镉（实验 1-3） 4-6)，交叉饲养的幼崽将在成年后进行血管内 (iv) 自行服用可卡因、海洛因或可卡因/海洛因组合 （速度球）。过期。 7-9 将确定产前、产后和 围产期镉暴露对大脑局部镉积累的影响 以及血液、肝脏、肾脏和骨骼（胫骨）中。因为铅存在于这些 药物滥用更常见的内城人口集中度较高，并且 因为美国超过 20% 的孕妇吸烟 含有很容易分布到胎儿/新生儿的镉， 拟议项目的结果应加强我们对可能的情况的理解 早期开发过程中的环境污染与药物之间的联系 在以后的生活中选择和使用。