It has been shown that rats, like humans, display individual differences in the propensity to develop psychostimulant self-administration. Animals showing the highest locomotor reactivity to novelty (HRs: High Responders) are more prone to develop amphetamine self-administration than rats having a low locomotor response to novelty (LRs: Low Responders). The present study was designed to ascertain whether individual differences are also present in the conditioning of drug effects, a process involved in the maintenance of addiction. After pairing the drug effect with a particular set of environmental cues, only HRs showed conditioned hyperlocomotion and environment-specific sensitization to the effect of amphetamine. Unconditioned sensitization was, however, observed in LRs but not in HRs. The environment-specific sensitization disappeared on extinction of the conditioned hyperlocomotion in HRs, indicating that conditioning facilitates the expression of sensitization. In contrast, an inhibitory influence of conditioning on sensitization emerged from the analysis of the same results over all the experimental groups, without taking individual differences into account. In conclusion, our results show that: (i) locomotor reactivity to novelty predicts both vulnerability to develop self-administration and contextual conditioning of drug effects, which suggests that the two phenomena are two related features and that conditioning plays an important role not only in the maintenance of drug intake but also in its development; (ii) conditioned and unconditioned sensitization can be developed separately in different individuals which suggests that they are independent phenomena; (iii) analysis of individual differences is relevant to pharmacological studies, especially with respect to drugs of abuse.