Document Detail


Chronic treatment with the D1 receptor antagonist, SCH 23390, and the D2 receptor antagonist, raclopride, in cebus monkeys withdrawn from previous haloperidol treatment. Extrapyramidal syndromes and dopaminergic supersensitivity.
MedLine Citation:
PMID:  7871047     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of chronic treatment with dopamine (DA) D1 and D2 receptor antagonists were evaluated in eight cebus apella monkeys with mild oral dyskinesia after previous haloperidol treatment. SCH 23390 (D1 antagonist) was given daily to investigate the direct behavioural effect during long-term treatment and the subsequent supersensitivity to DA agonists. Raclopride (D2 antagonist) was investigated for comparison. All drugs were given subcutaneously. SCH 23390 and raclopride induced dystonic syndromes, catalepsy, sedation and reduced locomotor activity. The monkeys developed marked tolerance to the dystonic effect of SCH 23390, while they showed increased sensibility to the dystonic effect of raclopride. Baseline oral dyskinesia (24 h after injection) remained unchanged during D1 antagonist treatment, while it increased during D2 antagonist treatment. SCH 23390 induced supersensitivity to the oral dyskinesia- and grooming-inducing effects of SKF 81297 (D1 agonist) after 9 weeks, while the subsequent treatment with raclopride induced supersensitivity to the reactivity- and stereotypy-inducing effects of quinpirole (D2 receptor agonist) after 3 weeks. Because of the possibility of a carry-over effect (SKF 81297-induced oral hyperkinesia and grooming), other changes in raclopride-induced behaviours cannot be ruled out. The development of tolerance to the dystonic effect of SCH 23390 and the unchanged baseline oral dyskinesia during SCH 23390 treatment indicate an advantageous profile of side effects of DA D1 receptor blockade.
Authors:
H Lublin; J Gerlach; L Peacock
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Psychopharmacology     Volume:  112     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  1993  
Date Detail:
Created Date:  1995-03-30     Completed Date:  1995-03-30     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  389-97     Citation Subset:  IM    
Affiliation:
St Hans Hospital, Department P, Roskilde, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Animals
Basal Ganglia Diseases / chemically induced,  physiopathology
Behavior, Animal / drug effects*
Benzazepines / pharmacology*
Cebus
Dopamine / physiology
Dose-Response Relationship, Drug
Female
Grooming / drug effects
Haloperidol / adverse effects*
Hypnotics and Sedatives / pharmacology
Male
Motor Activity / drug effects
Raclopride
Receptors, Dopamine D1 / agonists,  antagonists & inhibitors*
Receptors, Dopamine D2 / agonists,  antagonists & inhibitors*
Salicylamides / pharmacology*
Stereotyped Behavior / drug effects
Substance Withdrawal Syndrome / psychology*
Chemical
Reg. No./Substance:
0/Benzazepines; 0/Hypnotics and Sedatives; 0/Receptors, Dopamine D1; 0/Receptors, Dopamine D2; 0/Salicylamides; 52-86-8/Haloperidol; 84225-95-6/Raclopride

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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