Stimulation of D1 dopamine receptors reveals direct effects of the preferential dopamine autoreceptor agonist B-HT 920 on postsynaptic dopamine receptors.
Possible postsynaptic effects of the preferential dopamine autoreceptor agonist B-HT 920 were studied by means of the mouse motor activity. In reserpine-treated mice, B-HT 920 did not cause any motor activity by itself but it markedly potentiated the slight stimulating effect of the D1 dopamine agonist SKF 38 393. The effect was blocked by either the D2-receptor antagonist sulpiride or the D1-receptor antagonist SCH 23 390, indicating that motor activity is dependent on simultaneous activation of both dopamine receptor types. The hyperactivity produced by 0.1 mg kg-1 B-HT 920 in combination with SKF 38 393 in reserpine-treated mice was at least as great as that following a maximal dose of apomorphine, indicating that B-HT 920 is a full agonist at postsynaptic D2 receptors. The effect of 0.1 mg kg-1 B-HT 920 peaked earlier than those of 1 mg kg-1 and particularly, 10 mg kg-1 suggesting additional effects of the later two doses. B-HT 920 stimulates dopamine autoreceptors almost maximally following 0.1 or 1 mg kg-1 but only the latter dose (with or without SKF 38 393) caused hyperactivity of mice not treated with reserpine. This finding indicates that the postsynaptic D2 receptors are less sensitive to B-HT 920 than the D2 dopamine autoreceptors.
Andén
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NE
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Grabowska-Andén
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M
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage; D001381:Azepines / Q000008:administration & dosage*; D001552:Benzazepines / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D012110:Reserpine / Q000008:administration & dosage; D013469:Sulpiride / Q000008:administration & dosage
D001381:Azepines; D001552:Benzazepines; D011954:Receptors, Dopamine; D017981:Receptors, Neurotransmitter; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C024763:talipexole; D013469:Sulpiride; D012110:Reserpine; D001058:Apomorphine