The role of metabotropic glutamate receptors in addiction: Evidence from preclinical models

Addiction is a chronic disorder characterised by repeated bouts of drug taking, abstinence and relapse. The addicted state may be in part due to drug-induced neuroadaptations in the mesocorticolimbic and corticostriatal pathways. Recently focus has been on the role of aberrant glutamate transmission and its contribution to the hierarchical control over these systems. This review will expand our current knowledge of the most recent advances that have been made in preclinical animal models that provide evidence that implicate metabotropic glutamate receptors (mGluRs) in contributing to the neuroadaptations pertinent to addiction, as well as the role of Homer proteins in regulating these responses. The recent discovery of receptor mosaics will be discussed which add an additional dimension to the complexity of understanding the mechanism of glutamate mediated behaviours. Finally this review introduces a new area related to glutamatergic responses, namely microRNAs, that may become pivotal in directing our future understanding of how to best target intervention strategies to prevent addictive behaviours.

Research highlights
► Group I and II metabotrophic receptors (mGluR) are implicated in addictive behaviours.
► This involves regulation of synaptic plasticity, memory and learning.
► Regulation of mGluRs in these processes involves Homer and microRNAs.
► The complexity of mGluRs is heightened by their ability to form oligomers.
► Increasing our understanding of the role of mGluRs will aid in treating addiction.