Molecular Basis of Addiction: Conditioning and Relapse

成瘾的分子基础：调节和复发

• 批准号: 6753584
• 负责人: craig alexander schiltz
• 金额: $ 2.91万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6753584
• 关键词: SDS polyacrylamide gel electrophoresis; behavior test; behavioral /social science research tag; biological signal transduction; conditioning; craving; cues; drug addiction; gel mobility shift assay; gene expression; genetic regulation; laboratory rat; microarray technology; molecular psychobiology; morphine; nicotine; northern blottings; nucleus accumbens; predoctoral investigator; prefrontal lobe /cortex; relapse /recurrence; transcription factor; western blottings

DESCRIPTION (provided by applicant): The molecular and cellular basis for certain aspects of drug addiction is becoming well established. Researchers understand a great deal about how drugs operate at their primary targets, as well as how they bring about long-term cellular, molecular, and behavioral alterations. Noticeably missing, however, are effective treatments for addicted individuals. The challenge is to understand why relapse is so prevalent. One posited explanation for the high rates of relapse is the conditioning of effects of drugs. Drug-associated cues can evoke strong cravings in former drug users, and can be a powerful determinant of relapse to drug use. While this behavior is well characterized, very little is known about the cellular and molecular bases for drug-associated conditioned behavior. The proposed research will investigate the gene regulatory and signal transduction mechanisms involved in the expression of conditioned responses to an environment that had previously, repeatedly been paired with administration of morphine or nicotine, as well as how these relate to extinction of the conditioned responses. The guiding notion is that a better understanding of the basic cellular processes at work during the expression of drug-associated conditioned responses may lead to better treatments for addicted individuals.

描述（由申请人提供）： 药物成瘾某些方面的分子和细胞基础正在逐渐确立。研究人员非常了解药物如何作用于其主要靶点，以及它们如何带来长期的细胞、分子和行为改变。然而，明显缺乏对成瘾者的有效治疗。挑战在于理解为什么复发如此普遍。对于高复发率的一种假设解释是药物作用的调节。与毒品相关的线索可以唤起前吸毒者的强烈渴望，并且可能是吸毒复发的有力决定因素。虽然这种行为已得到很好的表征，但人们对药物相关条件行为的细胞和分子基础知之甚少。拟议的研究将调查对先前反复与吗啡或尼古丁给药配对的环境表达条件反应所涉及的基因调控和信号转导机制，以及这些机制与条件反应的消失有何关系。指导思想是，更好地了解药物相关条件反应表达过程中起作用的基本细胞过程可能会为成瘾个体带来更好的治疗。