Attenuation of precipitated morphine withdrawal symptoms by acute i.c.v. administration of a group II mGluR agonist

Br J Pharmacol. 1997 Jun;121(3):511-4. doi: 10.1038/sj.bjp.0701174.

Abstract

1. We previously showed that chronic i.c.v. antagonism of metabotropic glutamate receptors (mGluRs) concurrently with s.c. morphine significantly attenuated precipitated withdrawal symptoms. Conversely, acute i.c.v. injection of a selective group II mGluR antagonist just before the precipitation of withdrawal exacerbated abstinence symptoms. 2. In the present study, we showed that acute i.c.v. administration of the non-selective mGluR agonist 1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD), as well as the group II selective agonist (2S,1'R,2'R,3'R)-2-(2'.3'-dicarboxycyclopropyl)glycine (DCG-IV), significantly attenuated the severity of precipitated withdrawal symptoms. 3. From these results we hypothesize that chronic opioid treatment may indirectly induce a desensitization of group II mGluRs, which contributes to the development of dependence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Excitatory Amino Acid Agonists / administration & dosage*
  • Injections, Intraventricular
  • Male
  • Morphine / adverse effects*
  • Rats
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Substance Withdrawal Syndrome / drug therapy*

Substances

  • Excitatory Amino Acid Agonists
  • Receptors, N-Methyl-D-Aspartate
  • Morphine