Metabotropic glutamate receptors and opiate analgesia

Abstract

Morphine acts at μ-opioid receptors within the brain and spinal cord to induce analgesia. However, tolerance and dependence are potentially undesirable side effects encountered with repeated opiate administration. Opiate withdrawal, the physical correlate of dependence, is involved in the negative reinforcement of opiate addiction. Recently, blockers of ionotropic subtypes of glutamate receptors have been suggested to have therapeutical potential for opiate withdrawal. Fundytus and Coderre have also shown that antagonism of metabotropic glutamate receptors (mGluRs) and δ-opioid receptors can separately alleviate the behavioral symptoms of withdrawal. They propose that mGluRs and δ-opioid receptors share intermediates and products of the same second messenger pathways as μ-opioid receptors, thereby enhancing the desensitization of this receptor. Thus, mGluRs appear to be involved in the development of opiate tolerance and dependence and may provide a key target for adjunct therapy with opiate analgesia.