Psychopharmacology

, Volume 198, Issue 2, pp 271–278

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)

  • Bradford D. Fischer
  • Laurence L. Miller
  • Fredrick E. Henry
  • Mitchell J. Picker
  • Linda A. Dykstra
Original Investigation

Abstract

Rationale

Recent experimental data suggest that metabotropic glutamate receptor (mGluR) antagonists with selectivity for mGluR1 and mGluR2/3 enhance morphine-induced antinociception.

Objectives

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.

Results

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.

Conclusions

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.

Keywords

Metabotropic Glutamate NMDA Opioid Efficacy Antinociception 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Bradford D. Fischer
    • 1
  • Laurence L. Miller
    • 1
  • Fredrick E. Henry
    • 1
  • Mitchell J. Picker
    • 1
  • Linda A. Dykstra
    • 1
  1. 1.Department of PsychologyUniversity of North Carolina at Chapel HillChapel HillUSA

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