Amphetamine-enhanced accumulation of ( sup 3 H)-spiperone in mouse corpus striatum in vivo: Modification by other drugs

Journal Article · Sun Jan 01 00:00:00 EST 1989 · Proceedings of the Society for Experimental Biology and Medicine; (USA)

OSTI ID:7266889

Dorris, R L ^[1]

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1. Baylor College of Dentistry, Dallas, TX (USA)

Other investigators have reported that amphetamine administered to rodents results in an increase in the in vivo accumulation of either the tritiated dopamine receptor ligand, spiperone or pimozide in the dopaminergic corpus striatum, (specific binding) while not altering that in the sparsely dopaminergically innervated cerebellum (non-specific binding). Experiments were undertaken to determine if the results could be replicated and if some other drugs would modify the effect. Male mice were injected with ({sup 3}H)-spiperone (20 {mu}Ci/Kg, 0.0003 mg/kg) s.c. and killed 2 hrs later for determination of radioactivity in corpus striatum and cerebellum. Amphetamine (20 mg/kg, i.p.) given 15 min before ({sup 3}H)-spiperone, increased accumulation in striatum but not cerebellum. The increase was inhibited by {alpha} - methyltyrosine ({alpha}-MT), haloperidol, reserpine or amantadine. It is suggested that the amphetamine-induced increase in accumulation of ({sup 3}H)-spiperone in corpus striatum (specific binding) depends on release of large amounts of dopamine, which then must be able to interact with the dopamine receptor. The antagonism of the effect by {alpha}-MT or reserpine can be explained by dopamine depletion, that of haloperidol by antagonism for binding at the receptor site. It is suggested that amantadine acts by a dual mechanism: (1) as a low efficacy agonist, it competes for binding to the receptor and (2) it has some ability to block dopamine release.

• OSTI ID: 7266889
• Journal Information: Proceedings of the Society for Experimental Biology and Medicine; (USA), Vol. 191:1; ISSN 0037-9727
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AMPHETAMINES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BRAIN
DOPAMINE
IN VIVO
MICE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
ANALEPTICS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
DRUGS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
REACTION KINETICS
RODENTS
SYMPATHOMIMETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques