In vivo modulation of brain dopamine recognition sites: a possible model for emission computed tomography studies.

The content of authentic 3H-spiroperidol and of its metabolites was measured in brain regions of rat, guinea pig and mouse receiving tracer doses of 3H-spiroperidol intravenously (0.2 to 0.5 micrograms/kg). The time course of the 3H-spiroperidol content of various brain regions shows that a steady state was maintained between 2 and 6 hrs; the lowest 3H-spiroperidol content was attained in cerebellum where the value approached that of blood plasma. Since the cerebellum contains an insignificant number of dopamine receptors but many serotonin receptors and other sites that bind 3H-spiroperidol, the 3H-spiroperidol contained in cerebellum was considered background binding. In the striatum and olfactory tubercle of rats receiving two daily doses for 3 weeks of haloperidol or amphetamine the amount of 3H-spiroperidol that binds in vivo is decreased or increased, respectively. If the kinetic characteristics of in vivo binding of 3H-spiroperidol observed in the rat, guinea pig and mouse can be replicated in man using spiroperidol containing a gamma- or a position-emitting label, one might have a probe to study dopamine receptors in vivo with emission computed tomography scanning.