3HDihydrotetrabenazine, a New In Vitro Monoaminergic Probe for Human Brain

The monoamine transporter of dopamine (DA), noradrenaline, and 5-hydroxytryptamine synaptic vesicles was assayed in rat and human brain homogenates by in vitro binding of 3Hdihydrotetrabenazine. 3HReserpine, a second ligand of the vesicular monoamine transporter, could not be used. 3HDihydrotetrabenazine binding in rat brain was stable after 72 h at 22 degrees C postmortem. In major human brain regions, 3Hdihydrotetrabenazine binding was specific and saturable (KD, 2.7 nM). Displacement constants by substrates or inhibitors of vesicular monoamine uptake, and regional distribution in human brain were similar to those found in rodents. The highest densities of binding sites were observed in caudate nucleus, putamen, and accumbens nucleus. In caudate nucleus and in putamen from normal human subjects, 3Hdihydrotetrabenazine binding and homovanillic acid concentration were significantly or nearly significantly correlated. A weaker correlation was found between 3Hdihydrotetrabenazine binding and DA, in association with a higher variability of DA. 3HDihydrotetrabenazine binding in caudate nucleus and in putamen decreased significantly with age, unlike DA and homovanillic acid concentrations. The results establish 3Hdihydrotetrabenazine as a presynaptic monoaminergic ligand of interest for studies on postmortem human brain.