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

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.