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Journal of Neuroscience, Vol 5, 1513-1521, Copyright © 1985 by Society for Neuroscience
Differential visualization of dopamine and norepinephrine uptake sites in rat brain using [3H]mazindol autoradiography
JA Javitch, SM Strittmatter and SH Snyder
Mazindol is a potent inhibitor of neuronal dopamine (DA) and norepinephrine
(NE) uptake. DA and NE uptake sites in rat brain have been differentially
visualized using [3H]mazindol autoradiography. At appropriate
concentrations, desipramine (DMI) selectively inhibits [3H]mazindol binding
to NE uptake sites without significantly affecting binding to DA uptake
sites. The localization of DMI-insensitive specific [3H] mazindol binding,
reflecting DA uptake sites, is densest in the caudate-putamen, the nucleus
accumbens, the olfactory tubercle, the subthalamic nucleus, the ventral
tegmental area, the substantia nigra (SN) pars compacta, and the anterior
olfactory nuclei. In contrast, the localization of DMI-sensitive specific
[3H]mazindol binding, representing NE uptake sites, is densest in the locus
coeruleus, the nucleus of the solitary tract, the bed nucleus of the stria
terminalis, the paraventricular and periventricular nuclei of the
hypothalamus, and the anteroventral thalamus. The distribution of DMI-
insensitive specific [3H]mazindol binding closely parallels that of
dopaminergic terminal and somatodendritic regions, while the distribution
of DMI-sensitive specific [3H]mazindol binding correlates well with the
regional localization of noradrenergic terminals and cell bodies. Injection
of 6-hydroxydopamine, ibotenic acid, or colchicine into the SN decreases
[3H]mazindol binding to DA uptake sites in the ipsilateral caudate-putamen
by 85%. In contrast, ibotenic acid lesions of the caudate-putamen do not
reduce [3H]mazindol binding to either the ipsilateral or contralateral
caudate-putamen. Thus, the DA uptake sites in the caudate-putamen are
located on the presynaptic terminals of dopaminergic axons originating from
the SN.
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