Studies conducted with nonhuman laboratory animals have consistently shown that atypical
antipsychotics that are mixed
dopamine and
serotonin antagonists attenuate the discriminative-stimulus effects of
amphetamine. In the present experiment, eight healthy humans learned to discriminate 15 mg of oral
d-amphetamine. After acquiring the discrimination (i.e., > or = 80% correct responding on four consecutive days), the effects of a range of doses of
d-amphetamine (0, 2.5, 5, 10, and 15 mg), alone and after pretreatment with
risperidone (0 and 1 mg), a D2
dopamine and
5-hydroxytryptamine (5-HT)2
serotonin antagonist, were assessed.
d-Amphetamine alone functioned as a discriminative stimulus and produced stimulant-like self-reported
drug effects (e.g., increased ratings of "like
drug"). These effects were generally a function of dose.
Risperidone alone did not occasion
d-amphetamine-appropriate responding, but impaired performance.
Risperidone pretreatment significantly attenuated the discriminative-stimulus effects of
d-amphetamine, and some of the self-reported
drug effects. The results of the present experiment suggest that combining
drug-discrimination and self-reported
drug-effect questionnaires may be an effective strategy for assessing the behavioral effects of agonist-antagonist interactions. Future studies should compare the behavioral effects of
d-amphetamine after pretreatment with a selective D2
dopamine (e.g.,
haloperidol) or 5-HT2
serotonin (e.g.,
ritanserin) antagonist to determine the relative contribution of
dopamine and
serotonin systems in mediating the behavioral effects of stimulants in humans. The results of these studies might guide the development of a
pharmacotherapy for the treatment of
amphetamine abuse/dependence.