A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder

Abstract

Psychostimulant Use Disorder (PUD) is a chronic relapsing disorder with high motivation for drug abuse. In addition to developing PUD, the use of psychostimulants is a growing public health concern because it is associated with several physical and mental health impairments. To date, there are no FDA-confirmed medicines for the treatment of psychostimulant abuse; therefore, clarification of the cellular and molecular alterations participating in PUD is crucial for developing beneficial medications. PUD causes extensive neuroadaptations in glutamatergic circuitry involved in reinforcement and reward processing. These adaptations include both transient and long-lasting changes in glutamate transmission and glutamate receptors, especially metabotropic glutamate receptors, that have been linked to developing and maintaining PUD. Here, we review the roles of all groups of mGluRs,including I,II, and III in synaptic plasticity within brain reward circuitry engaged by psychostimulants (cocaine, amphetamine, methamphetamine, and nicotine). The review concentrates on investigations of psychostimulant-induced behavioral and neurological plasticity, with an ultimate goal to explore circuit and molecular targets with the potential to contribute to the treatment of PUD.

Keywords: Metabotropic glutamate receptor; Psychostimulant use disorder; Reward circuit; Synaptic plasticity.