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.
Original language | English (US) |
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Pages (from-to) | 271-278 |
Number of pages | 8 |
Journal | Psychopharmacology |
Volume | 198 |
Issue number | 2 |
DOIs | |
State | Published - Jun 2008 |
Externally published | Yes |
Keywords
- Antinociception
- Efficacy
- Glutamate
- Metabotropic
- NMDA
- Opioid
ASJC Scopus subject areas
- Pharmacology