Genomic Analysis of Avoidance Learning in Addiction

文摘:

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.