The role of multiple dopamine receptors in apomorphine and N-n-propylnorapomorphine-induced climbing and hypothermia.
Apomorphine and N-n-propylnorapomorphine (NPA) were compared for their ability to induce stereotyped cage climbing and hypothermia in mice. Climbing behavior was produced by similar doses of apomorphine and NPA (0.625-2.5 mg/kg s.c.), whereas NPA was 43 times more potent than apomorphine in inducing a hypothermic response. SKF38393 caused a shift to the left in the dose-response curve for NPA-induced climbing, the ED50 changing from 0.98 to 0.014 mg/kg. SKF38393 had no effect on apomorphine-induced climbing behaviour. The climbing response produced by apomorphine was antagonised by both D-1 and D-2 antagonists. Climbing behaviour induced by NPA (2.5 mg/kg) could be antagonised by SCH23390 but not by clebopride, however climbing behaviour induced by a low dose of NPA (0.06 mg/kg) plus SKF38393 could be blocked by both D-1 and D-2 receptor antagonists. The hypothermic responses produced by either apomorphine or NPA could only be reversed by the selective D-2 antagonist, clebopride. These results demonstrate that dopamine agonist-induced stereotyped cage climbing requires both D-1 and D-2 receptor stimulation, whereas the hypothermic response is D-2-mediated. The results also show that it is possible to assess the relative activity of a dopamine agonist at D-1 or D-2 receptors in vivo by comparing the ability of the compound to induce hypothermia and climbing behaviour.
Lilly Research Centre, Eli Lilly and Co., Windlesham, Surrey U.K.
N A
NA
Moore
M S
MS
Axton
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D051379:Mice; D019257:Quinpirole; D011954:Receptors, Dopamine / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects*
D001549:Benzamides; D001552:Benzazepines; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; C009074:N-n-propylnorapomorphine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C014417:clebopride; D001058:Apomorphine