Inhibition of circling behavior by neuroleptic drugs in mice with unilateral 6-hydroxydopamine lesions of the striatum.
The development of circling behavior to apomorphine, amphetamine and L-Dopa in mice with unilateral 6-hydroxydopamine lesions of the dopaminergic nerve terminals in the striatum has been studied, and the effect of a range of neuroleptic and sedative drugs on this circling behaviour has been investigated. Circling induced by all the stimulant drugs was inhibited in a dose-dependent manner by haloperidol, pimozide, chlorpromazine, metoclopramide and clozapine (in descending rank order of potency), but not by phenoxybenzamine, diazepam, promethazine and pentobarbitone sodium. This relatively simple animal model appears useful for screening neuroleptic drugs which may block striatal dopamine receptors, thereby predicting their potency to cause unwanted extrapyramidal effects but not their antipsychotic efficacy.
D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D001519:Behavior / Q000187:drug effects*; D001679:Biogenic Amines / Q000032:analysis; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000032:analysis / Q000187:drug effects*; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors; D003975:Diazepam / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D006892:Hydroxydopamines / Q000494:pharmacology; D007980:Levodopa / Q000037:antagonists & inhibitors; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010424:Pentobarbital / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011398:Promethazine / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*; D014149:Tranquilizing Agents / Q000494:pharmacology*
D001679:Biogenic Amines; D006892:Hydroxydopamines; D014149:Tranquilizing Agents; D010643:Phenoxybenzamine; D010868:Pimozide; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D007980:Levodopa; D011398:Promethazine; D010424:Pentobarbital; D003024:Clozapine; D006220:Haloperidol; D008787:Metoclopramide; D001058:Apomorphine; D003975:Diazepam; D003913:Dextroamphetamine; D002746:Chlorpromazine; D004298:Dopamine