Characterisation of the mechanisms by which purported dopamine agonists reduce spontaneous locomotor activity of mice.
The spontaneous locomotor activity of mice, recorded in the first 20 min period after placement in individual cages fitted with photocells, was reduced dose-dependently by apomorphine, (-)-N-n-propylnorapomorphine, 2-dimethylamino-5,6-dihydroxytetralin (M-7), 2-di-n-propylamino-5,6-dihydroxytetralin, (3,4-dihydroxyphenylamino)-2-imidazoline (DPI), N-n-propyl-benzo(f) and (g) quinolines, bromocriptine, N-n-propyl-3-(3-hydroxyphenyl)-piperidine (3-PPP) and by the N,N-dimethyl-, -diethyl-, -dipropyl- and -dibutyl-dopamines. SK&F 38393, in a wide dose range, failed to modify spontaneous locomotion. The inhibition of spontaneous locomotion caused by 2-di-n-propylamino-5,6-dihydroxytetralin was reversed by spiroperidol, haloperidol, benperidol and (-)-sulpiride, used in doses which did not in themselves modify spontaneous locomotion, but not by similarly selected doses of trifluperidol, fluphenazine, oxiperomide, molindone, thioridazine, prazosin, picrotoxin, methysergide, yohimbine, propranolol, phentolamine, atropine or SK&F 38393. Spiroperidol was also shown to reduce the actions of N,N-diethyl-, N,N-dipropyl- and N,N-dibutyl-dopamine, M-7, bromocriptine, apomorphine and, less markedly, 3-PPP and the (f) and (g)benzoquinolines, but not the actions of N,N-dimethyldopamine or DPI. Yohimbine reversed the action of DPI but ont that of any other purported dopamine agonist, whilst prazosin was ineffective throughout the experiments. The neuroleptic agents did not in themselves cause significant increase in spontaneous locomotor activity. Data is discussed in terms of a dopamine-neuroleptic sensitive mechanism for motor inhibition.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D048288:Imidazolines; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D014150:Antipsychotic Agents; D002395:Catecholamines; D048288:Imidazolines; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D015016:Yohimbine; D001971:Bromocriptine; D013134:Spiperone; C009074:N-n-propylnorapomorphine; C015842:2-(N,N-dipropyl)amino-5,6-dihydroxytetralin; C011775:(3,4-dihydroxyphenylamino)-2-imidazoline; D001058:Apomorphine; D004298:Dopamine; D011224:Prazosin