mGluR-Dependent Synaptic Plasticity in Drug-Seeking

A primary feature of drug addiction is the compulsive use despite negative consequences. A general consensus is emerging on the capacity of addictive substances to co-opt synaptic transmission and synaptic plasticity in brain circuits which are involved in reinforcement and reward processing. A current hypothesis is that drug-driven neuroadaptations during learning and memory processes divert the functions of these brain circuits, eventually leading to addictive behaviors. Metabotropic glutamate receptors (mGluRs) not only lead to long-term modulation of synaptic transmission but they have been implicated in drug-evoked synaptic plasticity and drug-seeking behaviors in two important ways. mGluR-dependent modulation of synaptic transmission is impaired by drug experience but interestingly their activation has been indicated as a strategy to restore baseline transmission after drug-evoked synaptic plasticity. Here we focus on the cellular mechanisms underlying mGluR-dependent long-term changes of excitatory synapses, and review results implicating these receptors in drug-evoked synaptic plasticity.