Differences in locomotor response to an inescapable novel environment have previously been shown to predict sensitivity to amphetamine reward, where high responders (HR), compared to low responders (LR), showed greater initial sensitivity to amphetamine self-administration. The present experiments sought to extend these findings and assessed the relationship between locomotor response to an inescapable novel environment and conditioned taste aversion (CTA) with amphetamine and lithium chloride (LiCl). Male Sprague–Dawley rats were tested for their locomotor response to an inescapable novel environment and divided into high (HR) or low (LR) responders, based on whether their locomotor scores were above or below the median activity level of the subject sample. After several days, the animals were tested in a CTA procedure and conditioned with either amphetamine or lithium chloride. Compared to HR rats, LR rats showed greater sensitivity to amphetamine CTA at the doses tested. In contrast, the results with LiCl showed no relationship between locomotor response to an inescapable novel environment and CTA. Taken together, the present results suggest that LR, compared to HR, rats show less sensitivity to the rewarding effects of amphetamine because they are more sensitive to aversive effects of amphetamine, as reflected in CTA. In contrast, HR rats display less sensitivity to aversive effects of amphetamine, which may explain their greater propensity to self-administer amphetamine.