INDIVIDUAL DIFFERENCES IN BIO-BEHAVIORAL DRUG RESPONSE

描述：（申请人摘要） 本研究将探讨行为指标的生物学相关性 与药物滥用的脆弱性有关。 药物滥用是一种复杂的相互作用 在文化、社会和心理风险因素中，但生物风险因素 其他因素也发挥了作用。 对危险因素的研究包括实验 研究生物和行为之间联系的策略 人类的依赖指数。 以前的PET研究表明， 额叶皮层和边缘系统的葡萄糖代谢降低， 与药物诱发的欣快症有关 药物强化研究 表明，有很大的差异，主观反应， 安非他明和选择重新体验其影响的倾向。 大约一半的测试正常人表现出积极的情绪增强， 安非他明并选择自己服用而不是安慰剂。 另一半 显示消极情绪增加，并选择自我管理安慰剂， 安非他明 第一项研究提出， 对大脑葡萄糖代谢产生不同的影响， 受影响的地区或地区。 我们预测， 在施用以下药物后，大脑将显示代谢率降低 安非他明在那些安非他明作为阳性兴奋剂的人中 然而，在这些患者中将观察到不同的代谢变化模式， 他们觉得它的效果令人厌恶。 第二项研究旨在扩大 大鼠临床前研究的结果显示， 反应性预测安非他明作用的个体差异 与脆弱性有关。 本研究将探讨 对新环境的反应（反应性），安非他明对 活动水平，对听觉刺激的反应，神经递质和 神经激素水平，以及这些不同的反应是否反过来预测 主观和强化效应的个体差异 安非他明 了解与脆弱性有关的生物差异 通过允许一种识别 高风险个体和治疗，通过提供 药物开发。

DESCRIPTION: (Applicant's Abstract) This research will investigate biological correlates of behavioral indices related to drug abuse vulnerability. Drug abuse is a complex interaction among cultural, social, and psychological risk factors, but biological factors also play a role. Research on risk factors includes experimental strategies that examine associations betweem biological and behavioral indices of dependence in humans. Previous PET studies have suggested that decreased glucose metabolism in the frontal cortex and limbic system are associated with drug-induced euphoria. Drug reinforcement studies have shown that there are large differences in subjective responses to amphetamine and the propensity to choose to reexperience its effects. Approximately half of tested normals show a positive mood enhancement to amphetamine and choose to self-administer it over placebo. The other half show negative mood increases and choose to self-administer placebo over amphetamine. The first study proposes to determine whether amphetamine produces differential effects on brain glucose metabolism, either in magnitude or regions affected. We predict that specific regions of the brain will show decreases in metabolic rate following the administration of amphetamine in those for whom amphetamine serves as positive reinforcer whereas a different pattern of metabolic changes will be observed in those who find its effects aversive. The second study is designed to extend findings from preclinical studies in rats showing that high levels of reactivity predict individual differences in the effects of amphetamine related to vulnerability. This study will examine the relationships among responses to a novel environment (reactivity), the actions of amphetamine on activity levels, reactions to auditory stimuli, neurotransmitter and neurohormonal levels, and whether these different responses in turn predict individual differences in the subjective and reinforcing effects of amphetamine. A knowledge of biological differences related to vulnerability can be useful for prevention efforts, by allowing a means of recognizing high risk individuals, and treatment, by providing a rationale for medication development.