TY - JOUR
T1 - Supraspinal administration of opioids with selectivity for μ-, δ- and κ-opioid receptors produces analgesia in amphibians
AU - Stevens, Craig W.
AU - Rothe, Kelly S.
N1 - Funding Information:
We thank Lisa L. Deason, M.S. for technical assistance and Leslie C. Newman, M.S., for help with the manuscript. Supported by research grants from the National Institutes of Health (NIDA 07326) and the Whitehall Foundation and by a training grant from Gardner Spring Co. We acknowledge our respective offspring for their inspiration.
PY - 1997/7/16
Y1 - 1997/7/16
N2 - 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.
AB - 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.
KW - Acetic acid test
KW - Amphibian
KW - Intracerebroventricular (i.c.v.) administration
KW - Opioid analgesia
KW - Rana pipiens
UR - http://www.scopus.com/inward/record.url?scp=0030858936&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(97)01026-1
DO - 10.1016/S0014-2999(97)01026-1
M3 - Article
C2 - 9274924
AN - SCOPUS:0030858936
SN - 0014-2999
VL - 331
SP - 15
EP - 21
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -