Motor actions of 7-OH-DPAT in normal and reserpine-treated mice suggest involvement of both dopamine D2 and D3 receptors.
In non-habituated mice, 7-hydroxy-N,N-di-n-propylaminotetralin (7-OH-DPAT, 0.04-10 mg/kg s.c.) potently and rapidly suppressed species-typical behaviours and induced frozen postures, with only occasional evidence of weak behavioural stimulation occurring at 5-10 mg/kg. This inhibitory effect was reversed by the dopamine D1 receptor agonist 2,3,4,5-tetrahydro-7,8-di-hydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF 38393, 10 mg/kg i.p.). 7-OH-DPAT (3-10 mg/kg) did not reinstate locomotion in 4 h habituated mice, either when administered alone or in conjunction with a threshold dose of SKF 38393 (3 mg/kg). By contrast, 7-OH-DPAT (0.2-10 mg/kg) dose-dependently reversed the akinesia of 24 h reserpine-treated mice. This response was blocked by the dopamine D2 receptor antagonist raclopride (10 mg/kg i.p.), but not by the dopamine D1 receptor antagonist (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepine-7-ol hemimaleate (SCH 23390, 0.05 mg/kg i.p.), and was potentiated synergistically by coinjection of SKF 38393 (3 mg/kg). These and earlier data suggest the motor inhibitory effects of 7-OH-DPAT (low doses) in normal animals are mediated by dopamine autoreceptors (D2 and/or D3), whilst its motor stimulant actions in normal (high doses) and in dopamine-depleted, supersensitive animals, are mediated by dopamine D2 receptors.
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006185:Habituation, Psychophysiologic; D007274:Injections, Intraperitoneal; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D050637:Receptors, Dopamine D3; D012110:Reserpine / Q000008:administration & dosage / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D001552:Benzazepines; D018491:Dopamine Agonists; C493594:Drd3 protein, mouse; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D012110:Reserpine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin