Conditioned cues and the expression of stimulant sensitization in animals and humans

Repeated intermittent exposure to psychostimulants can lead to long-lasting sensitization of the drugs' behavioral and biochemical effects. Such findings have figured importantly in recent theories of drug addiction proposing that sensitized nucleus accumbens (NAcc) dopamine (DA) overflow in particular acts in concert with other alterations in the neurochemistry of this nucleus to promote drug seeking and self-administration. Yet, experiments in rodents, non-human primates and humans have not always detected behavioral or biochemical sensitization following drug exposure, bringing into doubt the utility of this model. In an effort to reconcile apparent discrepancies in the literature, this review assesses conditions that might affect the expression of sensitization during testing. Specifically, the role played by conditioned cues is reviewed. A number of reports strongly support a potent and critical role for conditioned stimuli in the expression of sensitization. Findings suggest that stimuli associated either with the presence or absence of drug can respectively facilitate or inhibit sensitized responding. It is concluded that the presence or absence of such stimuli during testing for sensitization in animal and human studies could significantly affect the results obtained. It is necessary to consider this possibility especially when interpreting the results of studies that fail to observe sensitized responding.