![]() |
|
|
SC Roerig, RG Hoffman, AE Takemori, GL Wilcox and JM Fujimoto
Research Service, Veterans Administration Medical Center, Milwaukee, Wisconsin.
Concurrent administration of morphine sulfate i.c.v. and i.t. produces a multiplicative interaction for analgesia in the tail flick response in mice. This interaction decreases to an additive interaction in mice which are tolerant to s.c. morphine. To test the responses of opioids selective for mu or delta receptors, the present study examined the interactions between fentanyl citrate (mu agonist) and D-Ala2-D-Leu5 enkephalin (DADLE, a relatively selective delta agonist) administered i.c.v. and i.t. using the tail flick test in control and morphine pellet-implanted mice. A method was developed for assigning statistical significance to the resulting ED50 values when analyzed isobolographically. When fentanyl or DADLE was administered i.c.v. plus i.t., an additive interaction between sites occurred in control animals, which changed to an antagonistic interaction for fentanyl and a multiplicative interaction for DADLE after morphine pellet treatment. When morphine was given i.c.v. along with i.t. fentanyl or DADLE in control animals, multiplicative interactions occurred when equipotent doses were given. Thus, opioids which were more receptor-selective than morphine did not produce multiplicative interactions, but were multiplicative when given with morphine. These results suggest that activation of combinations of receptors (by morphine) was required for the multiplicative interaction. The supraspinal site involved mu receptors (which are not self-sufficient and require an additional component) and the spinal site involved mu or delta receptors. The use of isobolographic analysis required that the drugs, when administered concurrently at two sites, be given in a constant dose ratio.
This article has been cited by other articles:
![]() |
M. Terashvili, L. F. Tseng, H.-e. Wu, J. Narayanan, L. M. Hart, J. R. Falck, P. F. Pratt, and D. R. Harder Antinociception Produced by 14,15-Epoxyeicosatrienoic Acid Is Mediated by the Activation of {beta}-Endorphin and Met-Enkephalin in the Rat Ventrolateral Periaqueductal Gray J. Pharmacol. Exp. Ther., August 1, 2008; 326(2): 614 - 622. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. L. Cichewicz and E. A. McCarthy Antinociceptive Synergy between Delta 9-Tetrahydrocannabinol and Opioids after Oral Administration J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1010 - 1015. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Riba, Y. Ben, A. P. Smith, S. Furst, and N. M. Lee Morphine Tolerance in Spinal Cord Is Due to Interaction between {micro}- and delta -Receptors J. Pharmacol. Exp. Ther., January 1, 2002; 300(1): 265 - 272. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. W. Hurley, T. S. Grabow, R. J. Tallarida, and D. L. Hammond Interaction Between Medullary and Spinal delta 1 and delta 2 Opioid Receptors in the Production of Antinociception in the Rat J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 993 - 999. [Abstract] [Full Text] |
||||
![]() |
L. He and N. M. Lee Delta Opioid Receptor Enhancement of Mu Opioid Receptor-Induced Antinociception in Spinal Cord J. Pharmacol. Exp. Ther., June 1, 1998; 285(3): 1181 - 1186. [Abstract] [Full Text] |
||||