The ups and downs of addiction: role of metabotropic glutamate receptors

Trends Pharmacol Sci. 2004 May;25(5):265-72. doi: 10.1016/


Drug addiction is characterized by drug-induced positive affect, followed by withdrawal-associated negative affect. Such drug-induced positive and negative affective states provide crucial sources of motivation that drive compulsive drug consumption. Metabotropic glutamate (mGlu) receptors, which are responsible for slow glutamate-mediated neurotransmission, are located throughout limbic and cortical brain regions that are implicated in drug addiction. Emerging evidence indicates that mGlu receptors regulate many behavioral actions of addictive drugs. In particular, group I mGlu receptors play an important role in regulating the reinforcing effects of drugs of abuse. Furthermore, group II mGlu receptors have been implicated in the synaptic adaptations that occur in response to chronic drug exposure and contribute to the aversive behavioral syndrome observed during withdrawal. These findings increase our understanding of the pathological processes that are associated with the development of drug addiction, and might ultimately lead to new therapies for the treatment of this disorder.

Publication types

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

MeSH terms

  • Brain / drug effects*
  • Brain / metabolism
  • Humans
  • Receptors, Metabotropic Glutamate* / agonists
  • Receptors, Metabotropic Glutamate* / physiology
  • Substance Abuse, Intravenous
  • Substance-Related Disorders / metabolism*


  • Receptors, Metabotropic Glutamate