Synergistic blockade of some dopamine-mediated behaviours by (-)-sulpiride and SCH 23390 in the rat. 1989

R Dall'Olio, and P Roncada, and A Vaccheri, and O Gandolfi, and N Montanaro
Institute of Pharmacology, University of Bologna, Italy.

Several studies have indicated that the D2 dopamine receptors mediate the antidopaminergic activity of the neuroleptics; nevertheless, the selective blocker (-)-sulpiride weakly inhibits dopamine-mediated behaviour. The present study investigated whether the concomitant injection of doses of the D1 antagonist SCH 23390, which by themselves are without effect, would enable (-)-sulpiride to express fully neuroleptic activity in the rat. The benzamide YM 09151-2 that strongly inhibits dopamine-mediated behaviour was also studied. Rats receiving different doses of (-)-sulpiride, YM 09151-2 and SCH 23390 given alone or in combination were tested for exploratory activity, apomorphine-induced stereotyped behaviour and hyperactivity elicited by the D2 agonist LY 171555. When given alone, (-)-sulpiride (10, 20 and 40 mg/kg IP) had no effect on exploratory activity and stereotypy. When (-)-sulpiride was administered in combination with an ineffective dose of SCH 23390 (5 micrograms/kg) both responses were significantly inhibited. The combined administration of subthreshold doses of (-)-sulpiride (2.5 mg/kg) and SCH 23390 (2.5 micrograms/kg) significantly inhibited hypermotility induced by LY 171555. Moreover, the combined administration of ineffective doses of YM 09151-2 with subthreshold doses of SCH 23390 strongly inhibited all the behavioural responses. The results indicate that SCH 23390 allowed (-)-sulpiride to exhibit a wider spectrum of neuroleptic activity and potentiated the antidopaminergic activity of YM 09151-2.

UI MeSH Term Description Entries
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004873 Ergolines A series of structurally-related alkaloids that contain the ergoline backbone structure. Ergoline
D005106 Exploratory Behavior The tendency to explore or investigate a novel environment. It is considered a motivation not clearly distinguishable from curiosity. Curiosity,Novelty-Seeking Behavior,Behavior, Exploratory,Behavior, Novelty-Seeking,Behaviors, Exploratory,Behaviors, Novelty-Seeking,Curiosities,Exploratory Behaviors,Novelty Seeking Behavior,Novelty-Seeking Behaviors
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001058 Apomorphine A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. Apokinon,Apomorphin-Teclapharm,Apomorphine Chloride,Apomorphine Hydrochloride,Apomorphine Hydrochloride Anhydrous,Apomorphine Hydrochloride, Anhydrous,Apomorphine Hydrochloride, Hemihydrate,Britaject,Apomorphin Teclapharm
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors

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