Metabotropic glutamatergic receptors and their ligands in drug addiction

Pharmacol Ther. 2014 Jun;142(3):281-305. doi: 10.1016/j.pharmthera.2013.12.012. Epub 2013 Dec 19.


Glutamatergic excitatory transmission is implicated in physiological and pathological conditions like learning, memory, neuronal plasticity and emotions, while glutamatergic abnormalities are reported in numerous neurological and psychiatric disorders, including neurodegenerative diseases, epilepsy, stroke, traumatic brain injury, depression, anxiety, schizophrenia and pain. Also, several lines of evidence have accumulated indicating a pivotal role for glutamatergic neurotransmission in mediating addictive behaviors. Among the proteins regulating glutamatergic transmission, the metabotropic glutamate receptors (mGluR) are being developed as pharmacological targets for treating many neuropsychiatric disorders, including drug addiction. In this review we describe the molecular structure of mGluRs and their distribution, physiology and pharmacology in the central nervous system, as well as their use as targets in preclinical studies of drug addiction.

Keywords: Drug addiction; Glutamate; Metabotropic glutamatergic receptors; Relapse; Reward; Withdrawal.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Glutamic Acid / metabolism
  • Humans
  • Ligands
  • Receptors, Metabotropic Glutamate / analysis
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / physiology*
  • Substance-Related Disorders / drug therapy
  • Substance-Related Disorders / etiology*


  • Ligands
  • Receptors, Metabotropic Glutamate
  • Glutamic Acid