Intracellular actions of metabotropic glutamate receptors (mGluRs) are mediated by G-protein. mGluRs are divided into three groups, mGluI–mGluIII, based on signal transduction pathways and sequence homology (Schoepp 2001). Group I mGluRs (i.e., mGlu1/5 receptors) are predominantly postsynaptic, whereas group II (i.e., mGlu2/3 receptors) agonists have been shown to reduce glutamate release via a presynaptic mechanism (Schoepp 2001). GRM8 is a member of group III. Similar to group II agonists, group III agonists can negatively modulate glutamate transmission (Pothecary and others 2002). GRM8 mRNA has been detected in the cerebral cortex, hippocampus, lateral reticular nucleus of the thalamus, and retina (Duvoisin and others 1995; Saugstad and others 1997). Electrophysiological and morphological studies suggested that the mGluR8 receptor is localized at the presynaptic grid of glutamate synapses, and it functions as a presynaptic autoreceptor controlling glutamate release from the lateral perforant path terminals in the dentate gyrus (Shigemoto and others 1997). mGluR8-expressing nerve terminals have also been found to target subsets of GABAergic neurons in the hippocampus (Ferraguti and others 2005). Substances acting as agonists of group III mGlu receptors were shown
