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Original Article
Neuropsychopharmacology (1999) 20 340-345.10.1038/sj.npp.1395309

Effects of Atypical Antipsychotic Drug Treatment on Amphetamine-Induced Striatal Dopamine Release in Patients with Psychotic Disorders

Alan Breier MD, Tung-Ping Su MD, Anil K Malhotra MD, Igor Elman MD, Caleb M Adler MD, Neil I Weisenfeld BSE and David Pickar MD
Experimental Therapeutics Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

Correspondence: Dr Alan Breier, Eli Lilly and Co., Drop Code 0538 Lilly Corporate Center, Indianapolis, IN 46285

ABSTRACT

Clozapine, risperidone, and other new "atypical" antipsychotic agents are distinguished 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 atypical profile. In this study, we examined the effects of clozapine and risperidone on amphetamine-induced striatal dopamine release in patients with psychotic disorders. A novel 11C-raclopride/PET paradigm was used to derive estimates of amphetamine-induced changes in striatal synaptic dopamine concentrations and patients were scanned while antipsychotic drug-free and during chronic treatment with either clozapine or risperidone. We found that amphetamine produced significant reductions in striatal 11C-raclopride binding during the drug-free and antipsychotic drug treatment phases of the study which reflects enhanced dopamine release in both conditions. There were no significant differences in % 11C-raclopride changes between the two conditions indicating that these atypical agents do not effect amphetamine-related striatal dopamine release. The implications for these data for antipsychotic drug action are discussed.

Keywords: Clozapine; Risperidone; Positron emission tomography; Raclopride; Schizophrenia
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