SUPRASPINAL ADMINISTRATION OF OPIOIDS WITH SELECTIVITY FOR MU-OPIOID,DELTA-OPIOID AND KAPPA-OPIOID RECEPTORS PRODUCES ANALGESIA IN AMPHIBIANS

Previous results using an amphibian model showed that systemic and spi nal administration of opioids selective for mu, delta and kappa-opioid receptors produce analgesia. It is not known whether non-mammalian ve rtebrates also contain supraspinal sites mediating opioid analgesia. T hus, opioid agonists selective for mu (morphine; fentanyl), delta (DAD LE, [D-Ala(2), D-Leu(5)]-enkephalin; DPDPE, [D-Pen(2), D-Pen(5)]-enkep halin) and kappa (U50488, -N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneace tamide methanesulfonate; CI977, (5R)-(544 alpha, 744 alpha,845 nyl)-1- oxaspiro[4,5]dec-8yl]-4-benzofuranacetamide monohydrochloride) opioid old receptors were tested for analgesia following i.c.v. administratio n 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 block ed analgesia produced by i.c.v. morphine (10 nmol). ED50 values for th e six opioids ranged from 2.0 for morphine to 63.9 nmol for U50488. Th e rank order of analgesic potency was morphine > DADLE > DPDPE > CI977 > fentanyl > U50488. These results show that supraspinal sites mediat e opioid analgesia in amphibians and suggest that mechanisms of supras pinal opioid analgesia may be common to all vertebrates. (C) 1997 Else vier Science B.V.