No elevated D2 dopamine receptors in neuroleptic-naive schizophrenic patients revealed by positron emission tomography and [11C]N-methylspiperone

Abstract

The dopamine hypothesis of schizophrenia received strong support when a two- to three-fold elevation of D2 receptor densities was demonstrated by positron emission tomography (PET) and [11C]N-methylspiperone ([11C]NMSP). In the present study, the reproducibility of this finding was examined by application of a similar method in seven normal comparison subjects and seven neuroleptic-naive schizophrenic patients examined by PET before and after administration of haloperidol, 7.5 mg. After haloperidol, the specific binding of [11C]NMSP was reduced by 80-90%, resulting in a signal-to-noise ratio that was unfavorably low for reliable quantification. No significant difference was found between normal subjects and patients in a descriptive analysis of the time-activity curves or in a nonequilibrium graphical determination of D2 receptor densities in the basal ganglia. The results are consistent with those of a previous quantitative PET study of [11C]raclopride binding, which showed normal densities of D2 receptors in the striatum of neuroleptic-naive schizophrenic patients.