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The role of multiple dopamine receptors in apomorphine and N-n-propylnorapomorphine-induced climbing and hypothermia.

Abstract
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.
AuthorsN A Moore, M S Axton
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 178 Issue 2 Pg. 195-201 (Mar 20 1990) ISSN: 0014-2999 [Print] Netherlands
PMID2184043 (Publication Type: Journal Article)
Chemical References
  • Benzamides
  • Benzazepines
  • Ergolines
  • Receptors, Dopamine
  • Quinpirole
  • N-n-propylnorapomorphine
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • clebopride
  • Apomorphine
Topics
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (pharmacology)
  • Animals
  • Apomorphine (analogs & derivatives, pharmacology)
  • Benzamides (pharmacology)
  • Benzazepines (pharmacology)
  • Body Temperature (drug effects)
  • Dose-Response Relationship, Drug
  • Ergolines (pharmacology)
  • Female
  • Mice
  • Quinpirole
  • Receptors, Dopamine (drug effects)
  • Stereotyped Behavior (drug effects)

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