Effects of atypical antipsychotic drug treatment on amphetamine-induced striatal dopamine release in patients with psychotic disorders

Clozapine, risperidone, and other new "atypical" antipsychotic agents are d istinguished from traditional neuroleptic drugs by having clinical efficacy with either no or low levels of extrapyramidal symptoms (EPS). Preclinical models have focused on striatal dopamine systems to account for their atyp ical profile. In this study, we examined the effects of clozapine and rispe ridone on amphetamine-induced striatal dopamine release in patients with ps ychotic disorders. A novel C-11-raclopride/PET paradigm was used to derive estimates of amphetamine-induced changes in striatal synaptic dopamine conc entrations and patients were scanned while antipsychotic drug-free and duri ng chronic treatment with either clozapine or risperidone. We found that am phetamine produced significant reductions in striatal C-11-raclopride bindi ng during the drug-free and antipsychotic drug treatment phases of the stud y which reflects enhanced dopamine release in both conditions. There were n o significant differences in % C-11-raclopride changes between the two cond itions indicating that these atypical agents do not effect amphetamine-rela ted striatal dopamine release. The implications for these data for antipsyc hotic drug action are discussed.