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

Journal Article · Tue Apr 01 04:00:00 EST 1986 · Ann. Neurol.; (United States)

DOI:https://doi.org/10.1002/ana.410190412· OSTI ID:5488813

Bennett, Jr, J P; Wooten, G F

Striatal particulate preparations, both from rats with lesion-induced striatal dopamine (DA) loss and from some striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased /sup 3/H-neuroleptic binding, which is interpreted to be the mechanism of denervation-induced behavioral supersensitivity to dopaminergic compounds. After intravenous /sup 3/H-spiperone (/sup 3/H-SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate-bound /sup 3/H-SP in dopamine-denervated compared with intact striata. /sup 3/H-SP in vivo binds to less than 10% of striatal sites labeled by /sup 3/H-SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of /sup 3/H-SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. /sup 3/H-SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of /sup 3/H-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.

• Research Organization: Univ. of Virginia School of Medicine, Charlottesville
• OSTI ID: 5488813
• Journal Information: Ann. Neurol.; (United States), Journal Name: Ann. Neurol.; (United States) Vol. 4; ISSN ANNED
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AUTORADIOGRAPHY
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DISEASES
DISTRIBUTION
DOPAMINE
DRUGS
FILTRATION
HYDROXY COMPOUNDS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
MUSCLES
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SEPARATION PROCESSES
SYMPATHOMIMETICS
TISSUE DISTRIBUTION
TRITIUM COMPOUNDS
VERTEBRATES