mGluR-Dependent Synaptic Plasticity in Drug-Seeking

Abstract

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.

Keywords: AMPA receptors; NMDA receptor; addiction; long-term depression; mGluR; synaptic plasticity.

Figure 1

The role of mGluR-LTD during drug-seeking. mGluR-I are mainly located at the postsynaptic membrane, while mGluR-II are mostly presynaptic. While mGluR-I-LTD has been extensively described as postsynaptic and occurring through the removal of AMPARs, mGluR-II LTD expression is presynaptic, involving a decrease in neurotransmitter release. Acute drug exposure or withdrawal abolishes mGluR-LTD in various structures including the BNST and the NAc (Top). On the other hand forms of mGluR-LTD are able to rescue drug-evoked synaptic plasticity and behavioral adaptations (Bottom).