Previous research using outbred rats indicates that individual differences in activity in a novel environment predict sensitivity to the reinforcing effect of psychostimulant drugs. The current study examined if the link between responses related to novelty and amphetamine self-administration is heritable. Twelve inbred rat strains were assessed for locomotor activity in a novel environment, preference for a novel environment, and intravenous amphetamine self-administration (acquisition, extinction and amphetamine-induced reinstatement). Strain differences were observed in activity in a novel environment, novelty preference and amphetamine self-administration, indicating a genetic influence for each of these behaviors. While there was no relation between activity in an inescapable novel environment and amphetamine self-administration, strain-dependent differences in novelty preference were positively correlated with the amount of amphetamine self-administered. There was also a positive correlation between the dose-dependent rate of amphetamine self-administration and magnitude of reinstatement. These results show that the activity in an inescapable novel environment and the preference for a novel environment are different genetically, and thus likely to reflect different behavioral constructs. Moreover, these results implicate a genetic influence on the relation between novelty seeking and stimulant self-administration, as well as on the relation between stimulant reward and reinstatement.