Regional study of 3H-spiperone binding and the dopamine-sensitive adenylate cyclase in rat brain.

The inhibition of ³H-spiperone binding in vitro was determined in homogenates of a number of rat brain regions by 2-amino-6,7-dihydroxytetralin (ADTN), a rigid dopamine analog, cinanserin, a 5-hydroxytryptamine (5-HT) blocker and (+)-butaclamol, a neuroleptic drug with high affinity for both dopamine and 5-HT receptors. ADTN was a potent displacer of ³H-spiperone in striatum, was less effective in the olfactory tubercle, substantia nigra and hypothalamis and displaced ³H-spiperone from hippocampus and several cerebral cortical regions only at concentrations greater than 10 μM. The regional effects of cinanserin in inhibiting ³H-spiperone binding were essentially the converse of those observed for ADTN. (+)-Butaclamol, on the other hand, displaced ³H-spiperone only slightly less potently in regions with a poor or no dopaminergic innervation as compared to regions with a rich innervation. When ADTN and cinanserin were used in combination to displace ³H-spiperone, the results were similar to those observed with (+)-butaclamol or high concentrations of dopamine as displacer, further supporting the hypothesis that ³H-spiperone binds to both 5-HT and dopamine receptors. ADTN displaceable ³H-spiperone binding, which defines the specific binding of the radiolabel to a dopamine component, was compared to the dopamine-stimulated adenylate cyclase in the different brain regions. The poor correlation between these two parameters suggest that the receptors determined by the ³H-spiperone binding assay and the dopamine-sensitive adenylate cyclase constitute two different dopamine receptor populations.