QUANTIFICATION OF NEURORECEPTORS IN THE LIVING HUMAN BRAIN .3. D-2-LIKE DOPAMINE-RECEPTORS - THEORY, VALIDATION, AND CHANGES DURING NORMAL AGING

Dopamine receptor density is believed to decline in normal aging. To t est this hypothesis, we measured the density of dopamine D-2-like rece ptors in vivo in the neostriatum of normal living humans by using the graphical method. This method determines the D-2-like dopamine recepto r density in the human brain with an occupying ligand (unlabeled halop eridol) and a radioligand (labeled 3-N-methylspiperone). The method wa s examined critically, and the assumptions underlying the method were shown to be valid. The validation included comparison of the represent ation of tracer metabolism by high-pressure liquid chromatography and model assays, calculation of the lumped constant D-w from the value of its components, and comparable tracer partition coefficients in vitro and in vivo. In error analysis, the method consistently performed as well as the direct least-squares regression at statistical noise level s appropriate for the tomograph used in these studies. The method reve aled that the density of the D-2-like receptors that bind haloperidol in the caudate nucleus of normal humans declined 1% per year after the age of 18 years.