Dopamine denervation does not alter in vivo 3 H‐spiperone binding in rat striatum: Implications for external imaging of dopamine receptors in Parkinson's disease

Dopamine denervation does not alter in vivo 3 H‐spiperone binding in rat striatum: Implications... Striatal particulate preparations, both from rats with lesion‐induced striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3H‐neuroleptic binding, which is interpreted to be the mechanism of denervation‐induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3H‐spiperone (3H‐SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate‐bound 3H‐SP in dopamine‐denervated compared with intact striata. 3H‐SP in vivo binds to less than 10% of striatal sites labeled by 3H‐SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3H‐SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3H‐SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3H‐SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo–administered 3H‐SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Neurology Wiley

Dopamine denervation does not alter in vivo 3 H‐spiperone binding in rat striatum: Implications for external imaging of dopamine receptors in Parkinson's disease

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Publisher
Wiley
Copyright
Copyright © 1986 American Neurological Association
ISSN
0364-5134
eISSN
1531-8249
DOI
10.1002/ana.410190412
Publisher site
See Article on Publisher Site

Abstract

Striatal particulate preparations, both from rats with lesion‐induced striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3H‐neuroleptic binding, which is interpreted to be the mechanism of denervation‐induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3H‐spiperone (3H‐SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate‐bound 3H‐SP in dopamine‐denervated compared with intact striata. 3H‐SP in vivo binds to less than 10% of striatal sites labeled by 3H‐SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3H‐SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3H‐SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3H‐SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo–administered 3H‐SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo.

Journal

Annals of NeurologyWiley

Published: Apr 1, 1986

References

  • Specific binding of ( 11 C)spiroperidol in rat brain in vivo
    Arnett, Arnett; Fowler, Fowler; Wolf, Wolf; MacGregor, MacGregor
  • Measurements in vivo of parameters of the dopamine system
    Friedman, Friedman; DeJesus, DeJesus; Revenaugh, Revenaugh; Dinerstein, Dinerstein
  • Dopamine receptor parameters detected by ( 3 H)spiperone depend on tissue concentration: analysis and examples
    Seeman, Seeman; Ulpian, Ulpian; Wreggett, Wreggett; Wells, Wells

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