Genomic Analysis of Avoidance Learning in Addiction

摘要： 一个人对滥用药物成瘾的倾向是强烈遗传的， 可卡因成瘾遗传性可能特别高。此外，大多数人暴露于 可卡因和其他药物滥用不会发展成依赖性，即使那些依赖性的人也可能 随着药物使用的经济、社会和医疗成本的攀升，最终停止或减少其使用。 可能会减缓或阻止从偶尔使用到习惯性使用的转变的一个因素是先天的厌恶 对可卡因的反应，个体之间差异很大，取决于特定的分子和 我们实验室正在研究的电路机制。目前的U01项目已经测试了800多个NIH 异质性股票（HS）大鼠的任务，测量回避反应可卡因，并发现 雌性HS大鼠的遗传性很高，但雄性大鼠的遗传性可以忽略不计。因此，我们建议将重点转移到 这项研究的剩余2年对雌性大鼠，同时也寻求额外的资金来测试 额外的雌性大鼠来弥补雄性大鼠，这些雄性大鼠可能不会对最终的 GWAS发现。

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.