K99/R00: “Genetic basis of opioid reward and aversion in mice.”
A current focus is to determine the genetic basis of the rewarding properties of opioids in mice by combining quantitative trait locus (QTL) analysis of conditioned place preference (CPP) and transcriptome analysis via RNA-sequencing in genetic reference populations that yield high resolution QTLs. This multi-pronged approach to gene mapping will accelerate the nomination of candidate genes for validation via direct gene targeting. We are dissecting multiple behaviors that are expressed during opioid administration and CPP in real time (locomotor, visits, visit time, ultrasonic vocalizations, placebo-like responses) and applying factor analysis toward defining behavioral sets and inferring motivational meaning of these factors. We will estimate heritability for these trait sets and apply QTL mapping toward those most influenced by genetic factors. Elucidating the genetic basis of the motivational properties of opioids and other drugs of abuse will have direct application toward preventative/treatment strategies of addiction in humans, toward other substances of abuse (ethanol and food), and toward other conditions affected by the mesocorticolimbic pathway (Parkinson’s, depression, schizophrenia).
