Stimulation of dopamine D2 receptors induces an analgesia involving an opioidergic but non enkephalinergic link.
In the hot plate test, the dopamine D2 receptor agonist RU 24926 as well as the mixed dopamine D1/D2 receptor agonist apomorphine dose dependently increased the nociceptive threshold of mice, as expressed by the jump latency. The dopamine D1 receptor agonist SKF 38393 was ineffective on this parameter. The effect of RU 24926 was antagonized by the dopamine D2 specific receptor antagonist sulpiride but not by the dopamine D1 specific receptor antagonist SCH 23390. It was not increased by SKF 38393. However, the effect of apomorphine was partially but significantly reduced by SCH 23390. Inhibitors of enkephalin-degrading peptidases (thiorphan and bestatin injected i.c.v. or acetorphan injected i.v.) did not potentiate the effect of apomorphine whereas the delta opioid antagonist IC 154, 129 did not reverse the apomorphine-induced analgesia. Finally, the effect of apomorphine was significantly decreased in mice rendered tolerant to morphine. It is concluded that, in mice, the antinociceptive effect induced by apomorphine results mainly from stimulation of D2 receptors. This stimulation probably involves an endogenous opioid, different from enkephalins, which acts at mu opioid receptors.
Michael-Titus
A
A
Unité de Neuropsychopharmacologie Expérimentale, U.R.A. 1170 du C.N.R.S., Faculté de Médecine and Pharmacie de Rouen, Saint-Etienne du Rouvray, France.
Bousselmame
R
R
Costentin
J
J
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000698:Analgesia; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D004723:Endorphins / Q000502:physiology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement; D010627:Phenethylamines / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D011957:Receptors, Opioid / Q000502:physiology; D017450:Receptors, Opioid, mu; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D004723:Endorphins; D004745:Enkephalins; D009292:Narcotic Antagonists; D010627:Phenethylamines; D011954:Receptors, Dopamine; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D004743:Enkephalin, Leucine; C025254:RU 24926; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; C036405:ICI 154129; D001058:Apomorphine