Supraspinal administration of opioids with selectivity for μ-, δ- and κ-opioid receptors produces analgesia in amphibians

Craig W. Stevens, Kelly S. Rothe

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33 Scopus citations


Previous results using an amphibian model showed that systemic and spinal administration of opioids selective for μ, δ and κ-opioid receptors produce analgesia. It is not known whether non-mammalian vertebrates also contain supraspinal sites mediating opioid analgesia. Thus, opioid agonists selective for μ (morphine; fentanyl), δ (DADLE, [D-Ala2, D-Leu5]-enkephalin; DPDPE, [D-Pen2, D-Pen5]-enkephalin) and κ (U50488, trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methanesulfonate; CI977, (5R)-(544α,744α,845β)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4,5]dec-8yl] -4-benzofuranacetamide monohydrochloride) opioid receptors were tested for analgesia following i.c.v. administration in the Northern grass frog, Rana pipiens. Morphine, administered at 0.3, 1, 3 and 10 nmol/frog, produced a dose-dependent and long-lasting analgesic effect. Concurrent naltrexone (10 nmol) significantly blocked analgesia produced by i.c.v. morphine (10 nmol). ED50 values for the six opioids ranged from 2.0 for morphine to 63.9 nmol for U50488. The rank order of analgesic potency was morphine > DADLE > DPDPE > CI977 > fentanyl > U50488. These results show that supraspinal sites mediate opioid analgesia in amphibians and suggest that mechanisms of supraspinal opioid analgesia may be common to all vertebrates.

Original languageEnglish
Pages (from-to)15-21
Number of pages7
JournalEuropean Journal of Pharmacology
Issue number1
Publication statusPublished - 16 Jul 1997



  • Acetic acid test
  • Amphibian
  • Intracerebroventricular (i.c.v.) administration
  • Opioid analgesia
  • Rana pipiens

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