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[ 3 H]Dihydrotetrabenazine, a New In Vitro Monoaminergic Probe for Human Brain
Author(s) -
Scherman Daniel,
Raisman Rita,
Ploska Alain,
Agid Yves
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb10583.x
Subject(s) - monoaminergic , putamen , vesicular monoamine transporter , caudate nucleus , homovanillic acid , chemistry , medicine , endocrinology , monoamine neurotransmitter , nucleus accumbens , dopamine , human brain , biology , neuroscience , biochemistry , receptor , serotonin
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 [ 3 H]dihydrotetrabenazine. [ 3 H]Reserpine, a second ligand of the vesicular monoamine transporter, could not be used. [ 3 H]Dihydrotetrabenazine binding in rat brain was stable after 72 h at 22°C postmortem. In major human brain regions, [ 3 H]dihydrotetrabenazine binding was specific and saturable ( K D , 2.7 n M ). 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, [ 3 H]dihydrotetrabenazine binding and homovanillic acid concentration were significantly or nearly significantly correlated. A weaker correlation was found between [ 3 H]dihydrotetrabenazine binding and DA, in association with a higher variability of DA. [ 3 H]Dihydrotetrabenazine binding in caudate nucleus and in putamen decreased significantly with age, unlike DA and homovanillic acid concentrations. The results establish [ 3 H]dihydrotetrabenazine as a presynaptic monoaminergic ligand of interest for studies on postmortem human brain.