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Vol. 295, Issue 3, 1223-1231, December 2000
Departments of Pharmacology (R.P.A., I.L., P.M.), Radiology
(H.F.K., M.-P.K.), and Psychiatry (I.L.), and Institute for
Neurological Sciences (G.D.S., I.L., P.M.), University of Pennsylvania
School of Medicine, Philadelphia, Pennsylvania
The regional distribution and cellular localization of dopamine D3
receptors in the rat brain was examined using quantitative autoradiography. [125I]7-OH-PIPAT bound in a saturable
and reversible manner and exhibited subnanomolar affinity for a single
population of GTP-insensitive sites. The pharmacological profile was
characteristic of cloned D3 receptors and nonspecific binding was
uniformly low. The highest levels of D3 receptors were measured in the
islands of Calleja, nucleus accumbens, ventral pallidum, substantia
nigra, and lobules 9 and 10 of the cerebellum. The high specific
activity of this ligand also allowed detection of D3 receptors in other
regions, including the serotonergic dorsal and median raphe nuclei,
indicating that the distribution of this receptor is more widespread
than previously appreciated. The cellular localization of D3 receptors in regions containing dopaminergic cells and terminals was examined by
discrete injection of neurotoxins. Lesion of dopaminergic neurons with
6-hydroxydopamine produced 50% decreases in
[125I]7-OH-PIPAT binding in the nucleus accumbens and
substantia nigra. Quinolinic acid lesion of neurons originating in the
nucleus accumbens also produced approximately 50% decreases in D3
receptors in the nucleus accumbens, substantia nigra, and ventral
pallidum. 5,7-Dihydroxytryptamine lesion of serotonergic cells
and processes produced no changes in [125I]7-OH-PIPAT
binding. These results demonstrate the presence of D3 receptors in
several brain regions not previously identified and suggest that D3
receptors are expressed at somatodendritic and terminal levels of both
dopaminergic and nondo-paminergic cells within the mesolimbic
dopamine system.
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