Antinociceptive effects of morphine and U-50,488H on vaginal distension in the anesthetized rat.
The antinociceptive activity of the kappa- and mu-opioid receptor agonists, (+/-)-U-50,488H and morphine, was examined in a vaginal distension model in anaesthetized female rats. Vaginal distension induced a reproducible cardiovascular response (CVR) which was inhibited in a dose related manner by morphine (0.03-1.0 mg/kg i.v., ED50 = 0.16 mg/kg) and (+/-)-U-50,488H (0.08-1.6 mg/kg i.v., ED50 = 0.49 mg/kg). Morphine (0.3 microg/rat) administered i.c.v. inhibited the CVR by 81.6 +/- 7.9% whereas (+/-)-U-50,488H (30-300 microg/rat) was inactive by this route. A low dose of naloxone (30 microg/kg i.v.) blocked the effect of morphine but not that of (+/-)-U-50,488H. The kappa-opioid antagonist, nor-binaltorphimine (10 mg/kg s.c.) abolished the response to (+/-)-U-50,488H but not that of morphine. This demonstrates that both central and peripheral mu-opioid receptors may be involved in morphine-induced antinociception whereas the kappa-opioid agonist, (+/-)-U-50,488H, blocks vaginal nociception by acting on peripheral kappa-opioid receptors.
Friese
N
N
Institut de Recherche Jouveinal, Fresnes, France.
Diop
L
L
Lambert
C
C
Rivière
P J
PJ
Dahl
S G
SG
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage*; D000698:Analgesia; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D004971:Estrus / Q000502:physiology; D005260:Female; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology; D014623:Vaginal Diseases / Q000503:physiopathology*
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine