Genomic Analysis of Avoidance Learning in Addiction

成瘾中回避学习的基因组分析

• 批准号: 10442869
• 负责人: THOMAS C JHOU
• 金额: $ 14.92万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2023-06-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10442869
• 关键词: Addictive Behavior; Animal Testing; Animals; Avoidance Learning; Behavior; Biological; Brain; Catheterization; Cocaine; Cocaine Dependence; DNA; Dependence; Disulfiram; Drug usage; Economics; Equipment; Female; Funding; Genetic; Genomics; Goals; Heritability; Holidays; Human Resources; Individual; Intravenous; Learning; Maintenance; Measures; Mediating; Medical Care Costs; Messenger RNA; Molecular; Nicotine; Nicotinic Receptors; Pharmaceutical Preparations; Phenotype; Punishment; Rattus; Research; Rewards; Running; Smoking Behavior; Testing; Therapeutic Uses; Time; United States National Institutes of Health; Work; addiction; alcohol response; alcohol seeking behavior; base; behavior test; cocaine exposure; cohort; drug of abuse; genome wide association study; genomic tools; laboratory equipment; male; prevent; response; social

Abstract: The propensity of an individual to become addicted to drugs of abuse is strongly heritable, and the heritability of cocaine addiction may be particularly high. Furthermore, most individuals exposed to cocaine and other drugs of abuse do not progress to dependence, and even those who do may eventually stop or reduce their usage as the economic, social, and medical costs of drug use climb. One factor that may slow or prevent the transition from occasional to habitual use is innate aversive response to cocaine, which vary widely between individuals, and depend on specific molecular and circuit mechanisms being studied in our lab. The current U01 project has tested over 800 NIH Heterogeneous Stock (HS) rats on a task that measures avoidance responses to cocaine, and found heritability to be high in female HS rats, but negligible in males. Hence, we propose to shift the focus of the remaining 2 years of this study toward female rats, while also seeking additional funds to test additional female rats to make up for the males that will likely not contribute significantly to eventual GWAS findings.

抽象的： 一个人滥用药物成瘾的倾向具有很强的遗传性，并且 可卡因成瘾的遗传性可能特别高。此外，大多数人暴露于 可卡因和其他药物滥用不会发展为依赖，即使是那些滥用的人也可能 随着吸毒的经济、社会和医疗成本上升，最终停止或减少吸毒。 可能减缓或阻止从偶尔使用到习惯使用的转变的一个因素是天生的厌恶 对可卡因的反应因人而异，并且取决于特定的分子和 我们实验室正在研究电路机制。目前U01项目已测试超过800个NIH 异质种群（HS）大鼠执行一项测量对可卡因的回避反应的任务，并发现 雌性 HS 大鼠的遗传力较高，但雄性大鼠的遗传力可以忽略不计。因此，我们建议转移焦点 这项研究剩余 2 年的研究对象是雌性大鼠，同时还寻求额外的资金来进行测试 额外的雌性老鼠来弥补雄性老鼠可能不会对最终的结果做出重大贡献 GWAS 发现。