The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction

Accumulating evidence suggests that glutamate, as one of the most important excitatory neurotransmitters in the brain, plays a key role in drug addiction including opioid addiction. There is substantial evidence for glutamatergic projections into mesocorticolimbic dopaminergic neurons, which are associated with opioid psychological dependence and are also the key regions of enhancement effect. Glutamate may be involved in the process of opioid addiction not only by acting on its ionotropic and metabotropic glutamate receptors that activate several signal transduction pathways, but also by interacting with other neurotransmitters or neuropeptides such as opioids, dopamine, gamma-aminobutyric acid and substance P in the mesocorticolimbic dopaminergic regions. Studies on the role of glutamate and its receptors in opioid addiction will provide a new strategy for the exploitation of drugs for the treatment of opioid addiction. (C) 2009 Elsevier Ltd. All rights reserved.