Locomotor behaviour of selective dopamine agonists in mice: is endogenous dopamine the only catecholamine involved?
The purpose of the study was to determine the effect alone and in combination of the selective dopamine (DA) agonists SKF 38393 (D1-) and B-HT 920 (D2-) on the locomotor activity of reserpine pretreated mice (5 mg kg-1 i.p.). After 4 h, reserpine-B-HT 920 (up to 20 mg kg-1 s.c.) did not induce locomotor activity whereas SKF 38393 was markedly effective at high doses (greater than or equal to 30 mg kg-1 s.c.). In contrast, at 24 h, reserpine-B-HT 920 (0.2-6 mg kg-1 s.c.) elicited considerable locomotor activity and SKF 38393 (1-100 mg kg-1 s.c.) was effective at lower doses when compared with the corresponding 4 h reserpine experiments. When, however, these animals additionally received alpha-methyl-p-tyrosine (alpha MPT; 300 mg kg-1 i.p., at 4 h before the DA agonists) neither B-HT 920 (0.2-20 mg kg-1 s.c.) nor SKF 38393 (1-100 mg kg-1 s.c.) had an effect of their own. When B-HT 920 was tested in the presence of a fixed-dose of SKF 38393 (10 or 3 mg kg-1 s.c., combination experiments) B-HT 920 (0.6-20 mg kg-1 s.c.) induced considerable locomotor activity at 4 h post reserpine. At 24 h post reserpine the dose-response curve of B-HT 920 (0.06-20 20 mg kg-1 s.c.) was shifted to the left and the maximum effect was greatly increased. When additional alpha MPT was given, the dose response curve was the same but the maximum effect was markedly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
Pichler
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L
Ernst-Boehringer-Institut für Arzneimittelforschung, Vienna, Austria.
Pifl
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002395:Catecholamines / Q000502:physiology*; D004298:Dopamine / Q000096:biosynthesis / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects; D019805:alpha-Methyltyrosine
D001381:Azepines; D002395:Catecholamines; D015259:Dopamine Agents; D008781:Methyltyrosines; D011954:Receptors, Dopamine; D019805:alpha-Methyltyrosine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C024763:talipexole; D004298:Dopamine