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Titolo:
WHY DOES CLOZAPINE STIMULATE THE MOTOR-ACTIVITY OF RESERPINE-PRETREATED RATS WHEN COMBINED WITH A DOPAMINE D-1 RECEPTOR AGONIST
Autore:
JACKSON DM; MOHELL N; BENGTSSON A; MALMBERG A;
Indirizzi:
ASTRA ARCUS AB,PRECLIN RES & DEV,DEPT BEHAV & BIOCHEM PHARMACOL S-15185 SODERTALJE SWEDEN PRECLIN RES & DEV,DEPT MOLEC PHARMACOL S-15185 SODERTALJE SWEDEN
Titolo Testata:
European journal of pharmacology
fascicolo: 1-3, volume: 282, anno: 1995,
pagine: 137 - 144
SICI:
0014-2999(1995)282:1-3<137:WDCSTM>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPLETED MICE; ANTAGONISTS; BRAIN; NEUROLEPTICS; BINDING; SITES;
Keywords:
DOPAMINE RECEPTOR AGONIST; CLOZAPINE; DOPAMINE D-1 RECEPTOR; DOPAMINE D-2 RECEPTOR; QUINPIROLE; ANTIPSYCHOTIC, ATYPICAL; SCOPOLAMINE; SKF38393; (RAT);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
D.M. Jackson et al., "WHY DOES CLOZAPINE STIMULATE THE MOTOR-ACTIVITY OF RESERPINE-PRETREATED RATS WHEN COMBINED WITH A DOPAMINE D-1 RECEPTOR AGONIST", European journal of pharmacology, 282(1-3), 1995, pp. 137-144

Abstract

The aim of the present experiments was to investigate the locomotor stimulant effects of the atypical antipsychotic agent, clozapine, in rats depleted of their dopamine by reserpine and cr-methyl-p-tyrosine pretreatment. Clozapine itself induced a slight but never significant stimulation of locomotor activity which was enhanced by the addition of the selective dopamine D-1 receptor agonist, SKF38393 trahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine), but not by the selective dopamine D-2 receptor agonist, quinpirole. The stimulation produced by clozapineplus SKF38393 was blocked by the selective dopamine D-1 receptor antagonist, SCH23390 (7-chloro-8-hydroxy-3-methyl-l-phenyl-2, hydrochloride), while the selective dopamine D-2 receptor antagonist, haloperidol,was ineffective. A combination of SCH23390 and haloperidol blocked the clozapine plus SKF38393-induced locomotion. Unlike clozapine, neither the selective 5-HT2 receptor antagonist, ritanserin, nor the dopamine D-2 receptor antagonists, haloperidol and remoxipride, caused locomotor activation when given alone or in combination with SKF38393. The indirectly acting sympathomimetic amine, d-amphetamine, was inactive inthe monoamine-depleted rats, indicating that no dopamine was available for release by d-amphetamine. The muscarinic receptor antagonist, scopolamine, alone did not alter locomotion, but produced marked stimulation when combined with SKF38393 but not with quinpirole. This stimulation was not affected by haloperidol. However, the scopolamine plus SKF38393-induced stimulation was partially blocked by SCH23390 or by a combination of haloperidol and SCH23390. The data indicate that clozapine, in rats depleted of their dopamine stores, exhibits properties consistent with those of a dopamine receptor agonist. The pharmacology ofthis behavioural stimulation was similar but not identical to that seen with the muscarinic receptor antagonist, scopolamine. The behavioural effects of clozapine reported here might be explained by a dual effect: antagonism of muscarinic receptors and agonist-like activity at dopamine receptors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 08:24:41