Sensation seeking is a personality trait characterized by risk-taking and the desire to experience novel stimuli. Evidence suggests that sensation seeking may increase an individual's psychological and neurobiological vulnerabilities to drug abuse. One potential animal model of human sensation seeking is high response to novelty in rats. High responders (HRs) prefer a novel environment to a familiar one and show an increase in locomotor activity in the new environment. These rats also show lower levels of anxiety-like behaviour on several tests. Furthermore, HRs display a much higher propensity to self-administer psychostimulants compared to low responders (LRs). HR rats and sensation seeking humans share a number of similarities, for instance both exhibit elevated mesolimbic dopamine activity, which has been implicated in central reward signaling and drug addiction. Evidence of common behavioural tendencies, physiological responses and gene expression patterns suggest that the HR model could be used as an animal model to investigate substance abuse in sensation seeking humans.