Increased efficacy of μ-opioid agonist-induced antinociception by metabotropic glutamate receptor antagonists in C57BL/6 mice: comparison with (−)-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid (LY235959)
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Recent experimental data suggest that metabotropic glutamate receptor (mGluR) antagonists with selectivity for mGluR1 and mGluR2/3 enhance morphine-induced antinociception.
The present study addressed the hypothesis that mGluR antagonists enhance opioid antinociception by increasing opioid efficacy.
Materials and methods
The antinociceptive effects of the partial μ-opioid receptor agonists buprenorphine and dezocine were first assessed in a hot-plate procedure under conditions of low (53°C) and high (56°C) stimulus intensity. Under conditions in which buprenorphine and dezocine produced submaximal antinociceptive effects, these drugs were assessed after pretreatment with the mGluR1 antagonist JNJ16259685, the mGluR5 antagonist MPEP, the mGluR2/3 antagonist LY341495, and for comparison, the N-methyl-D-aspartate (NMDA) receptor antagonist LY235959.
Buprenorphine (0.032–3.2 mg/kg) and dezocine (0.1–10 mg/kg) were fully efficacious at 53°C and produced submaximal antinociceptive effects at 56°C (i.e., their effects did not exceed 50% of the maximum possible effect). Pretreatment with JNJ16259685 (1.0–3.2 mg/kg), LY341495 (1.0–3.2 mg/kg), and LY235959 (0.32–1.0 mg/kg) enhanced the antinociceptive effects of buprenorphine and dezocine at 56°C, as revealed by significant increases in the peak effects of both drugs to ~100% maximum possible effect. In contrast, pretreatment with MPEP (1.0–3.2 mg/kg) did not modulate the antinociceptive effects of buprenorphine and dezocine.
These results suggest that, similar to the NMDA receptor antagonist LY235959, the mGluR1 antagonist JNJ16259685 and the mGluR2/3 antagonist LY341495 increase the antinociceptive efficacy of buprenorphine and dezocine.
- Allen RM, Dykstra LA (2001) N-methyl-D-aspartate receptor antagonists potentiate the antinociceptive effects of morphine in squirrel monkeys. J Pharmacol Exp Ther 298:288–297
- Alvarez FJ, Villalba RM, Carr PA, Grandes P, Somohano PM (2000) Differential distribution of metabotropic glutamate receptors 1a, 1b, and 5 in the rat spinal cord. J Comp Neurol 422:464–487 CrossRef
- Bond A, Lodge D (1995) Pharmacology of metabotropic glutamate receptor-mediated enhancement of responses to excitatory and inhibitory amino acids on rat spinal neurones in vivo. Neuropharmacology 34:1015–1023 CrossRef
- Bossard AE, Guirimand F, Fletcher D, Gaude-Joindreau V, Chauvin M, Bouhassira D (2002) Interaction of a combination of morphine and ketamine on the nociceptive flexion reflex in human volunteers. Pain 98:47–57 CrossRef
- Cao CQ, Evans RH, Headley PM, Udvarhelyi PM (1995) A comparison of the effects of selective metabotropic glutamate receptor agonists on synaptically evoked whole cell currents of rat spinal ventral horn neurones in vitro. Br J Pharmacol 115:1469–1474
- Carlton SM, Hargett GL, Coggeshall RE (2001) Localization of metabotropic glutamate receptors 2/3 on primary afferent axons in the rat. Neuroscience 105:957–969 CrossRef
- Cerne R, Randic M (1992) Modulation of AMPA and NMDA responses in rat spinal dorsal horn neurons by trans-1-aminocyclopentane-1,3-dicarboxylic acid. Neurosci Lett 144:180–184 CrossRef
- Chen SL, Huang EY, Chow LH, Tao PL (2005) Dextromethorphan differentially affects opioid antinociception in rats. Br J Pharmacol 144:400–404 CrossRef
- Dykstra LA (1990) Butorphanol, levallorphan, nalbuphine and nalorphine as antagonists in the squirrel monkey. J Pharmacol Exp Ther 254:245–252
- Fischer BD, Dykstra LA (2006) Interactions between an NMDA antagonist and low-efficacy opioid receptor agonists in assays of schedule-controlled responding and thermal nociception. J Pharmacol Exp Ther 318:1300–1306 CrossRef
- Fischer BD, Zimmerman EI, Picker MJ, Dykstra LA (2008) Morphine in combination with metabotropic glutamate receptor antagonists on schedule-controlled responding and thermal nociception. J Pharmacol Exp Ther 324:732–739 CrossRef
- Gharagozlou P, Demirci H, David Clark J, Lameh J (2003) Activity of opioid ligands in cells expressing cloned mu opioid receptors. BMC Pharmacol 3:1 CrossRef
- Hoskins PJ, Hanks GW (1991) Opioid agonist–antagonist drugs in acute and chronic pain states. Drugs 41:326–344 CrossRef
- Jia H, Rustioni A, Valtschanoff JG (1999) Metabotropic glutamate receptors in superficial laminae of the rat dorsal horn. J Comp Neurol 410:627–642 CrossRef
- Jones CK, Eberle EL, Peters SC, Monn JA, Shannon HE (2005) Analgesic effects of the selective group II (mGlu2/3) metabotropic glutamate receptor agonists LY379268 and LY389795 in persistent and inflammatory pain models after acute and repeated dosing. Neuropharmacology 49:206–218 CrossRef
- Kelso SR, Nelson TE, Leonard JP (1992) Protein kinase C-mediated enhancement of NMDA currents by metabotropic glutamate receptors in Xenopus oocytes. J Physiol 449:705–718
- King AE, Liu XH (1996) Dual action of metabotropic glutamate receptor agonists on neuronal excitability and synaptic transmission in spinal ventral horn neurons in vitro. Neuropharmacology 35:1673–1680 CrossRef
- Kozela E, Pilc A, Popik P (2003) Inhibitory effects of MPEP, an mGluR5 antagonist, and memantine, an N methyl-D-aspartate receptor antagonist, on morphine antinociceptive tolerance in mice. Psychopharmacology 165:245–251
- Morgan D, Cook CD, Smith MA, Picker MJ (1999) An examination of the interactions between the antinociceptive effects of morphine and various μ-opioids: the role of intrinsic efficacy and stimulus intensity. Anesth Analg 88:407–413 CrossRef
- Naisbitt S, Kim E, Tu JC, Xiao B, Sala C, Valtschanoff J, Weinberg RJ, Worley PF, Sheng M (1999) Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 23:569–582 CrossRef
- Nemmani KV, Grisel JE, Stowe JR, Smith-Carliss R, Mogil JS (2004) Modulation of morphine analgesia by site-specific N-methyl-D-aspartate receptor antagonists: dependence on sex, site of antagonism, morphine dose, and time. Pain 109:274–283 CrossRef
- Preston KL, Jasinski DR (1991) Abuse liability studies of opioid agonist–antagonists in humans. Drug Alcohol Depend 28:49–82 CrossRef
- Skeberdis VA, Lan J, Opitz T, Zheng X, Bennett MV, Zukin RS (2001) mGluR1-mediated potentiation of NMDA receptors involves a rise in intracellular calcium and activation of protein kinase C. Neuropharmacology 40:856–865 CrossRef
- Toll L (1995) Intact cell binding and the relation to opioid activities in SH-SY5Y cells. J Pharmacol Exp Ther 273:721–727
- Tu JC, Xiao B, Naisbitt S, Yuan JP, Petralia RS, Brakeman P, Doan A, Aakalu VK, Lanahan AA, Sheng M, Worley PF (1999) Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron 23:583–592 CrossRef
- Walker EA, Butelman ER, DeCosta BR, Woods JH (1993) Opioid thermal antinociception in rhesus monkeys: receptor mechanisms and temperature dependency. J Pharmacol Exp Ther 267:280–286
- Wessinger WD (1986) Approaches to the study of drug interactions in behavioral pharmacology. Neurosci Biobehav Rev 10:103–113 CrossRef
- Yoon MH, Choi J, Bae HB, Kim SJ, Chung ST, Jeong SW, Chung SS, Yoo KY, Jeong CY (2006) Antinociceptive effects and synergistic interaction with morphine of intrathecal metabotropic glutamate receptor 2/3 antagonist in the formalin test of rats. Neurosci Lett 394:222–226 CrossRef
- Increased efficacy of μ-opioid agonist-induced antinociception by metabotropic glutamate receptor antagonists in C57BL/6 mice: comparison with (−)-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid (LY235959)
Volume 198, Issue 2 , pp 271-278
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Industry Sectors