HEAVY METALS AND COCAINE--INTERACTIONS

重金属和可卡因——相互作用

基本信息

批准号：
2120361
负责人：
JACK R NATION
金额：
$ 17.16万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-09-30 至 1998-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2120361
关键词：
behavior test behavioral habituation /sensitization cadmium cocaine dopamine drug interactions laboratory rat lead microdialysis nucleus accumbens operant conditionings pharmacokinetics psychopharmacology self medication

项目摘要

Previous investigations have shown that recurrent exposure to dietary lead or cadmium results in an attenuated response to ip injections of cocaine HCL. Specifically, these metals reduced the psychostimulant effects of a 10mg/kg dose of cocaine HCL, but not a 20 or 40 mg/kg dose, in adult male rats. Because lead and cadmium are competitive with calcium, and inasmuch as calcium-mediation is central to the neurochemical and behavioral effects of cocaine, it is possible that these toxicants may attenuate the pharmacologic effects of cocaine. Relevant to this issue, four separate lines of investigation are proposed. Experiments 1 and 2 will examine the effects of chronic low- level exposure to lead or cadmium on the rate-dependent effects of acute cocaine exposure, in an operant context. The second series of experiments will assess the impact of lead (Exp. 3) or cadmium (Exp. 4) on the discriminative stimulus effects associated with cocaine. Experiments 5 and 6 will test for the rewarding effects of cocaine in lead-treated and cadmium-treated animals, using an intravenous self- administration paradigm. Also, the effects of lead (Exp. 7) or cadmium (Exp. 8) on cocaine-induced increases in extracellular levels of dopamine within the nucleus accumbens and prefrontal cortex will be determined, using a microdialysis technique. Finally, the effect of lead or cadmium on cocaine pharmacokinetics will be assessed (Exp. 9-10). In all experiments a full range of drug doses will be used. The results from this project will provide valuable information about the possible link between xenobiotic contamination and the response to a prominently abused psychoactive drug.

先前的研究表明，经常接触饮食铅或镉会导致腹腔注射的反应减弱可卡因盐酸盐。具体来说，这些金属减少了精神兴奋剂 10 毫克/千克剂量的盐酸可卡因的作用，但不是 20 或 40 毫克/千克剂量的作用，在成年雄性大鼠中。因为铅和镉具有竞争性钙，并且因为钙介导对于可卡因对神经化学和行为的影响，可能是这些毒物可能会减弱可卡因的药理作用。与这个问题相关，有四个独立的调查方向：建议的。实验 1 和 2 将检验慢性低血压的影响铅或镉的暴露水平对急性发作的速率依赖性影响在操作环境中接触可卡因。第二个系列实验将评估铅（实验 3）或镉（实验 4）的影响与可卡因相关的歧视性刺激效应。实验 5 和 6 将测试可卡因对人的奖励作用铅处理和镉处理的动物，使用静脉内自我行政范式。此外，铅（实验 7）或镉的影响（实验 8）可卡因诱导的细胞外多巴胺水平增加在伏隔核和前额皮质内将被确定，使用微透析技术。最后，铅或镉的影响将评估对可卡因药代动力学的影响（实验 9-10）。总共实验将使用全范围的药物剂量。结果来自该项目将提供有关可能的链接的有价值的信息外来物质污染与对严重滥用物质的反应之间的关系精神活性药物。