Discriminative Stimulus Effects of Psychostimulants.

Numerous drugs elicit locomotor stimulant effects at appropriate doses; however, we typically reserve the term psychostimulant to refer to drugs with affinity for monoamine reuptake transporters. This chapter comprises select experiments that have characterized the discriminative stimulus effects of psychostimulants using drug discrimination procedures. The substitution profiles of psychostimulants in laboratory rodents are generally consistent with those observed in human and nonhuman primate drug discrimination experiments. Notably, two major classes of psychostimulants can be distinguished as those that function as passive monoamine reuptake inhibitors (such as cocaine) and those that function as substrates for monoamine transporters and stimulate monoamine release (such as the amphetamines). Nevertheless, the discriminative stimulus effects of both classes of psychostimulant are quite similar, and drugs from different classes will substitute for one another. Most importantly, for both the cocaine-like and amphetamine-like psychostimulants, dopaminergic mechanisms most saliently determine discriminative stimulus effects, but these effects can be modulated by alterations in noradrenergic and serotonergic neurotransmission as well. Thusly, the drug discrimination assay is useful for characterizing the interoceptive effects of psychostimulants and determining the mechanisms that contribute to their subjective effects in humans.