Glutamate is a main excitatory neurotransmitter in the central nervous system, and it plays a role in learning, memory and neurotoxicity. The biological actions of glutamate are mediated by ionotropic and metabotropic glutamate receptors, which are ion channels and GPCRs respectively. Metabotropic glutamate receptors (mGluRs) are members of the class 3 G-protein coupled receptor family, which are characterized by a large extracellular domain. They are further classified into group I, II, and III mGluRs on the basis of their sequence identity, pharmacology, and signal transduction mechanism. Group I (mGlu1 and mGlu5) couple to the phospholipase C pathway through Galphaq, whereas group II (mGlu2 and mGlu3) and group III (mGlu4 , mGlu6 , mGlu7 , and mGlu8) negatively couple to the adenylyl cyclase pathway though Galphai (Conn and Pin, 1997). Agonists of the Group II metabotropic glutamate receptors, mGlu2 and mGlu3, display efficacy in animal models of anxiety and psychosis. A key role for mGlu2 in mediating these effects is indicated by the observation that selective allosteric potentiator of mGlu2 also retains antipsychotic-like activities in mice. In addition, mGlu2/3 agonists display analgesic activity in animal models.