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Dopamine receptor density is believed to decline in normal aging. To test this hypothesis, we measured the density of dopamine D 2 -like receptors in vivo in the neostriatum of normal living humans by using the graphical method. This method determines the D 2 -like dopamine receptor density in the human brain with an occupying ligand (unlabeled haloperidol) and a radioligand (labeled 3- N-methylspiperone). The method was examined critically, and the assumptions underlying the method were shown to be valid. The validation included comparison of the representation 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 levels appropriate for the tomograph used in these studies. The method revealed 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.

journal of cerebral blood flow and metabolism

Quantification of Neuroreceptors in the Living Human Brain: III. D<sub>2</sub>-Like Dopamine Receptors: Theory, Validation, and Changes during Normal Aging

Quantification of Neuroreceptors in the Living Human Brain: III. D2-Like Dopamine Receptors: Theory, Validation, and Changes during Normal Aging

Quantification of Neuroreceptors in the Living Human Brain: III. D₂-Like Dopamine Receptors: Theory, Validation, and Changes during Normal Aging