Genomic Analysis of Avoidance Learning in Addiction

摘要： 一个人对滥用药物上瘾的倾向是强烈可遗传的， 可卡因成瘾的遗传率可能特别高。此外，大多数接触过 可卡因和其他滥用药物不会发展为依赖，即使是那些依赖的人也可能 随着药物使用的经济、社会和医疗成本攀升，最终停止或减少它们的使用。 一个可能减缓或阻止从偶尔使用向习惯使用转变的因素是天生的厌恶 对可卡因的反应，个体差异很大，取决于特定的分子和 我们实验室正在研究电路机制。目前的U01项目已经测试了800多个NIH 异质库存(HS)大鼠在一项测量对可卡因的回避反应的任务中发现 雌性HS大鼠的遗传率很高，而雄性大鼠的遗传率可以忽略不计。因此，我们建议将重点转移 这项研究的剩余两年是针对雌性大鼠的，同时也在寻求额外的资金来测试 额外的雌性老鼠来弥补雄性老鼠，这些雄性老鼠最终可能不会对 Gwas的调查结果。

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.