Metabotropic Glutamate Receptors and Parkinson’s Disease: Basic and Preclinical Neuroscience

Since the late 1990s, data from various laboratories have provided strong evidence that the three groups of mGlu receptors are widely and specifically expressed in the basal ganglia (BG), where they modulate neuronal excitability as well as synaptic transmission and plasticity. Therefore, targeting specific mGlu receptor subtypes by means of selective drugs could be a possible strategy for restoring normal synaptic function and neuron activity in the BG in Parkinson’s disease (PD). In this context, the spectacular development of subtype-selective mGlu receptor agonists, antagonists, and allosteric modulators has provided scientists with a wide range of neuropharmacological tools that have largely supported this hypothesis. This review provides data showing that drugs acting on mGlu receptors can alleviate PD motor symptoms and reduce levodopa-induced dyskinesia in animal models of PD and recent clinical trials that confirm these findings.