Metabotropic glutamate receptors and opiate analgesia - Therapeutic implications

Morphine acts at mu-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 delta-opioid receptors can separately alleviate the behavioral symptoms of withdrawal. They propose that mGluRs and delta-opioid receptors share intermediates and products of the same second messenger pathways as mu-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.