Roles of metabotropic glutamate receptor 8 in neuropsychiatric and neurological disorders

Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors. Among eight mGlu subtypes (mGlu1-8), mGlu8 has drawn increasing attention. This subtype is localized to the presynaptic active zone of neurotransmitter release and is among the mGlu subtypes with high affinity for glutamate. As a Gi/o-coupled autoreceptor, mGlu8 inhibits glutamate release to maintain homeostasis of glutamatergic transmission. mGlu8 receptors are expressed in limbic brain regions and play a pivotal role in modulating motivation, emotion, cognition, and motor functions. Emerging evidence emphasizes the increasing clinical relevance of abnormal mGlu8 activity. Studies using mGlu8 selective agents and knockout mice have revealed the linkage of mGlu8 receptors to multiple neuropsychiatric and neurological disorders, including anxiety, epilepsy, Parkinson's disease, drug addiction, and chronic pain. Expression and function of mGlu8 receptors in some limbic structures undergo long-lasting adaptive changes in animal models of these disorders, which may contribute to the remodeling of glutamatergic transmission critical for the pathogenesis and symptomatology of brain illnesses. This review summarizes the current understanding of mGlu8 biology and the possible involvement of the receptor in several common psychiatric and neurological disorders.