Abstract
SCH 23390, an apparently selective antagonist of central D1 dopamine receptors, produced profound catalepsy at low doses (0.1 mg/kg, s.c.). Pretreatment with the selective D2 receptor agonists LY 141865, RU 24213 or LY 171555, the active (-) enantiomer of LY 141865, elicited a dose-dependent inhibition of the cataleptic response. Pergolide and apomorphine were also effective. This effect was not due to altered disposition or penetration of SCH 23390 into the brain since pretreatment with a dose of LY 171555 which completely blocked catalepsy had no effect on the ID50 of SCH 23390 to inhibit 3H-cis-piflutixol binding to D1 receptors measured ex vivo. Alternative mechanisms are considered to explain the results, which offer new insights into striatal dopaminergic regulation of motor activity.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apomorphine / pharmacology
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Benzazepines / antagonists & inhibitors*
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Benzazepines / pharmacology
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Binding, Competitive
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Catalepsy / chemically induced
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Catalepsy / physiopathology*
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Catalepsy / prevention & control
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Corpus Striatum / metabolism
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Dose-Response Relationship, Drug
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Ergolines / pharmacology
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Humans
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Male
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Motor Activity / drug effects*
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Pergolide
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Phenethylamines / pharmacology
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Quinpirole
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Rats
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Rats, Inbred Strains
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Receptors, Dopamine / drug effects*
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Receptors, Dopamine / metabolism
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Receptors, Dopamine D1
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Receptors, Dopamine D2
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Stereoisomerism
Substances
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Benzazepines
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Ergolines
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Phenethylamines
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Receptors, Dopamine
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Receptors, Dopamine D1
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Receptors, Dopamine D2
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Quinpirole
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Pergolide
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N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride
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Apomorphine