Evaluation of selective actions of dopamine D-1 and D-2 receptor agonists and antagonists on opioid antinociception.
The effect of the selective dopamine receptor agonists SKF 38393 (D-1) and quinpirole (D-2) on nociception was studied in the mouse tail immersion test. The D-1 receptor agonist induced mild hyperalgesia whereas the D-2 agonist produced antinociception. Pretreatment with either the selective D-1 receptor antagonist SCH 23390 or the D-2 receptor antagonist (-)-sulpiride converted the hyperalgesia produced by the D-1 agonist into an antinociceptive response whereas the effect of the D-2 receptor agonist was significantly antagonised. The antinociceptive response of selective opioid agonists was also studied in combination with selective dopamine receptor agonists and antagonists. Sufentanil (mu-opioid) antinociception was enhanced in animals pretreated with (-)-sulpiride but not SCH 23390. In animals co-administered sufentanil with SKF 38393 there was a reduced antinociceptive effect whilst quinpirole enhanced the action of sufentanil. Likewise, antinociception induced by the kappa-opioid agonist U50,488H was unaltered in animals pretreated with SCH 23390, increased by (-)-sulpiride, and reduced by SKF 38393. delta-Opioid antinociception induced by [D-Ala2,D-Leu5]enkephaline remained unmodified following pretreatment with either (-)-sulpiride or SCH 23390 but was potentiated in animals which received both the delta-agonist and the D-2 receptor agonist. It is concluded that D-2 receptor agonists not only have intrinsic antinociceptive activity, but can also potentiate opioid-induced antinociception. Similarly, dopamine D-2 receptor antagonists appear to potentiate opioid-induced antinociception in this nociceptive model.
Rooney
K F
KF
Division of Pharmacology, Welsh School of Pharmacy, Cardiff, U.K.
Sewell
R D
RD
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D015259:Dopamine Agents / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004873:Ergolines / Q000494:pharmacology; D005283:Fentanyl / Q000031:analogs & derivatives / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009294:Narcotics / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology; D019257:Quinpirole; D011930:Reaction Time / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D017409:Sufentanil; D013469:Sulpiride / Q000494:pharmacology
D015259:Dopamine Agents; D004873:Ergolines; D009294:Narcotics; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D019257:Quinpirole; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D017409:Sufentanil; D005283:Fentanyl