title: Blockade of the mGlu5 receptor decreases basal and stress-induced cortical norepinephrine in rodents.
abstract: BACKGROUND
  Glutamate, the major excitatory neurotransmitter in the brain mediates its effects by both ionotropic and metabotropic receptor subtypes. Recently, the search for selective ligands for glutamate receptor subtypes has led to the discovery of 2-methyl-6-(phenylethynyl)pyridine (MPEP), an antagonist specific for metabotropic glutamate receptor 5 (mGlu5). This receptor is highly expressed in limbic forebrain regions and is thought to modulate anxiety-related processes. The noradrenergic nucleus locus coeruleus (LC) is an important mediator of stress responses and dysfunction of this system is implicated in affective disorders such as anxiety and depression.
  
  
  OBJECTIVE
  We sought to assess the effects of mGlu5 receptor antagonists, MPEP and 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) on cortical norepinephrine (NE) levels.
  
  
  METHODS
  In vivo microdialysis and high-pressure liquid chromatography with electrochemical detection (HPLC-ED) were used to assess the effects of mGlu5 antagonism on extracellular NE in the frontal cortex, a major terminal field of the LC.
  
  
  RESULTS
  Blockade of the mGlu5 receptor elicited significant reductions in extracellular NE in the frontal cortex. The benzodiazepine diazepam also reduced cortical NE. Furthermore, MPEP administration attenuated stress-induced increases in extracellular NE.
  
  
  CONCLUSIONS
  Taken together, these data show that MPEP and MTEP, through their blockade of the mGlu5, reduce extracellular norepinephrine, the impact of which may contribute to their anxiolytic actions.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA. michelle.page@jefferson.edu
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Page
authors.forename: Paul
authors.initials: P
authors.lastname: Szeliga
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gasparini
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
mesh_terms: D000818:Animals; D003975:Diazepam / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005625:Frontal Lobe / Q000737:chemistry*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000032:analysis*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013315:Stress, Psychological / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; C121465:6-methyl-2-(phenylethynyl)pyridine; D003975:Diazepam; D009638:Norepinephrine