title: Novel metabotropic glutamate receptor 4 and glutamate receptor 8 therapeutics for the treatment of anxiety.
abstract: BACKGROUND
  The fast actions of the excitatory neurotransmitter glutamate are mediated by glutamate-gated ion channels (ionotropic Glu receptors). Metabotropic glutamate receptors (mGlus) are coupled to second messenger pathways via G proteins and modulate glutamatergic and GABAergic neurotransmission. Of the eight different types of mGlus (mGlu1-mGlu8), mGlu4, mGlu6, mGlu7 and mGlu8 are members of group III. Except for mGlu6, group III receptors are generally located presynaptically and regulate neurotransmitter release. Because of their role in modulating excitatory neurotransmission, mGlus are attractive targets for therapies aimed at treating anxiety disorders.
  
  
  METHODS
  In this review, the authors discuss the role of mGlu4 and mGlu8 in anxiety disorders. They also discuss how mGlu4 and mGlu8 have distinct expression patterns in the brain, which might have related functions. Finally, the authors discuss how compounds that target more than one mGlu receptor might be therapeutically more effective.
  
  
  CONCLUSIONS
  mGlu4 might compensate for mGlu8 deficiency, and deficiency of both receptors might result in a more pronounced phenotype than deficiency of either receptor alone. The distinct and overlapping anatomical distribution and functions of mGlu4 and mGlu8 suggest that both receptors, either individually or combined, are attractive therapeutic targets in anxiety disorders, post-traumatic stress disorder, Parkinson's disease, and multiple sclerosis.
authors.affiliation: Departments of Behavioral Neuroscience, Neurology, and Radiation Medicine, Oregon Health and Science University, Division of Neuroscience , ONPRC, Portland, OR , USA +1 503 494 1424 ; +1 503 494 6877 ; raberj@ohsu.edu.
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
authors.forename: Robert M
authors.initials: RM
authors.lastname: Duvoisin
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D018094:Receptors, Metabotropic Glutamate; C111435:metabotropic glutamate receptor 8; C108823:metabotropic glutamate receptor 4
keywords: allosteric modulators; anxiety; fear learning; metabotropic glutamate receptor