[3H]methoxytetrabenazine: a high specific activity ligand for estimating monoaminergic neuronal integrity.
(1995) Neuroscience — Vol. 68, n° 3, p. 955-962 (1995)
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- The properties as well as the distribution of high specific activity alpha-[O-methyl-3H]methyoxytetrabenazine binding to the synaptic vesicular monoamine transporter were studied autoradiographically in rat brain sections. Saturation analysis revealed [3H]methoxytetrabenazine interaction with a homogeneous population of striatal sites (Hill coefficient 1.00 +/- 0.05), with an apparent equilibrium dissociation binding constant of 3.9 +/- 0.4 nM and a maximal binding capacity of 1.2 +/- 0.1 fmol/micrograms protein. Highest levels of [3H]methoxytetrabenazine binding sites were observed in regions richly innervated by the monoamine systems. In the presence of 1 microM concentrations of a variety of competing drugs, only reserpine significantly inhibited [3H]methoxytetrabenazine binding. The presynaptic nigrostriatal location of [3H]methoxytetrabenazine binding was demonstrated by unilateral lesion of the median forebrain bundle with 6-hydroxydopamine. The resulting decrease of striatal [3H]methoxytetrabenazine binding showed an excellent correlation with tyrosine hydroxylase-positive neuron density in the substantia nigra pars compacta (r2 = 0.96; P < 0.001). The present studies demonstrate that in vitro [3H]methoxytetrabenazine binding is a reliable, quantitative marker of the synaptic vesicular monoamine transporter. Further, it is indicated that [3H]methoxytetrabenazine binding provides an accurate assessment of monoamine neuronal losses and may thus be of great value in future studies of neurodegenerative diseases.
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Vander Borght, T., Sima, A. A., Kilbourn, M. R., Desmond, T. J., Kuhl, D. E., & Frey, K. A. (1995). [3H]methoxytetrabenazine: a high specific activity ligand for estimating monoaminergic neuronal integrity. Neuroscience, 68(3), 955-962. https://hdl.handle.net/2078.5/73339 (Original work published 1995)