Identifying addiction related genes through operant sensation seeking in a BXD recombinant inbred panel.

Cocaine addiction is a global public health issue that affects millions of people worldwide. Like other diseases, it is influenced by genetic factors. As of now, multiple cocaine-addiction genes have identified, but many still remain undiscovered. Operant sensation seeking (aSS) is a mouse phenotypic assay that measures responses for novel, non-drug stimuli. It is hypothesized that mapping ass phenotypes can lead to the discovery of new addiction-related genes. This study utilizes previously collected and unpublished ass data from a BXD mouse panel to conduct quantitative trait locus (QTL) mapping. Using the publicly available resource GeneNetwork (www.genenetwork.org) and candidate gene prioritization criteria adapted from Lu et al 2008, we mapped QTLs and found candidate genes for ass phenotypes. We identified genome-wide significant QTL on chromosomes 4 and 13 associated with percentage of active lever presses and non-directed lever pressing, respectively. We then utilized publicly available gene expression data from the nucleus accumbens (NAc), midbrain, and prefrontal cortex (PFC) of mice to identify Ccnl2 as a positional candidate for the chromosome 4 QTL. Similarly, we identified Arsk and Pou5f2 as positional candidates for the chromosome 13 QTL. These data illuminate novel genes for sensation seeking that may be implicated in the onset and persistence of addiction. Additionally, these findings further the claim that ass is a viable tool for studying addiction genetics