Differential labeling of dopamine and sigma sites by [ 3H]nemonapride and [ 3H]raclopride in postmortem human brains

Abstract

The difference between the binding of [ 3H]nemonapride and [ 3H]raclopride has been used to quantify dopamine D 4 receptors in postmortem schizophrenic brain studies. Recent work, however, has suggested that at least part of the differential between [ 3H]nemonapride and [ 3H]raclopride binding may represent σ rather than D 4 receptor sites. We applied the nemonapride-raclopride subtraction method to postmortem, non-schizophrenic human striatum to examine the variation in dopaminergic receptor binding labeled by these ligands. Variation in σ receptor binding labeled by [ 3H]nemonapride was studied in frontal cortex, striatum and cerebellum. Specific binding was defined by sulpiride (dopamine receptor ligand), PPAP ( σ receptor ligand) and haloperidol (mixed dopaminergic/ σ agent), respectively. Haloperidol defined a combination of sites, which were approximately the sum of the dopaminergic and σ components defined by sulpiride and PPAP, respectively. Significant inter-individual variation in the amount of specific binding for dopaminergic and σ receptor sites was observed. However, no significant nor consistent observation of striatal dopamine D 4 receptors or D 4-like binding sites was observed in the striatum even though two independent sets of tissues, with different dissections were used. The inconsistencies in some previous postmortem studies appear to be at least partially explained by the inclusion of both σ and dopaminergic components in [ 3H]nemonapride binding and the inherent high inter-individual variability of the different components.