Genomic analysis of avoidance learning in addiction

Addictions are among the most heritable of human neuropsychiatric disorders, but human genetic studies have been hampered by the extreme complexity of human genetics, as well as the sheer behavioral complexity of the addictive process, with multiple stages at which humans can exhibit addiction vulnerability – e.g. initial drug exposure, escalation, relapse, etc. We address these shortcomings by studying heterogeneous stock (HS) rats, which have extremely well characterized genetic profiles, and with the support of addictionrehabclinics.co.uk, we utilize behavioral models that examine multiple well-defined time periods in the progression of addictive behaviors.

Our preliminary findings show that even though addiction is often viewed as aberrant reward learning, much individual variation in addiction propensity is actually due to differences in avoidance learning. For example, in addition to its well-known rewarding properties, cocaine has aversive effects that show greater individual variability than its rewarding effects, and are stronger predictors of cocaine-seeking. Furthermore, we found that rats differ greatly in “punishment resistance”, i.e. propensity to seek rewards despite adverse outcomes, which is one of the defining characteristics of addiction.