title: Postsynaptic mGluR mediated excitation of neurons in midbrain periaqueductal grey.
abstract: Metabotropic glutamate (mGlu) receptors modulate pain from within the midbrain periaqueductal grey (PAG). In the present study, the postsynaptic mGlu receptor mediated effects on rat PAG neurons were examined using whole-cell patch-clamp recordings in brain slices. The selective group I agonist DHPG (10 μM) produced an inward current in all PAG neurons tested which was associated with a near parallel shift in the current-voltage relationship. By contrast, the group II and III mGlu receptor agonists DCG-IV (1 μM) and l-AP4 (3 μM) produced an outward current in only 10-20% of PAG neurons tested. The DHPG induced current was concentration dependent (EC(50) = 1.4 μM), was reduced by the mGlu1 antagonist CPCCOEt (100 μM), and was further reduced by CPCCOEt in combination with the mGlu5 antagonist MPEP (10 μM). The glutamate transport blocker TBOA (30 μM) also produced an inward current, however, this was largely abolished by CNQX (10 μM) plus AP5 (25 μM). Slow EPSCs were evoked following train, but not single shock stimulation, which were enhanced by TBOA (30 μM). The TBOA enhancement of slow EPSCs was abolished by MPEP plus CPCCOEt. These findings indicate that endogenously released glutamate, under conditions in which neurotransmitter spill-over is enhanced, activates group I mGlu receptors to produce excitatory currents within PAG. Thus, postsynaptic group I mGlu receptors have the potential to directly modulate the analgesic, behavioural and autonomic functions of the PAG. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
authors: Pain Management Research Institute, Level 13, Kolling Building, Kolling Institute of Medical Research, Northern Clinical School, The University of Sydney at Royal North Shore Hospital, St Leonards, NSW, Australia.
authors: Adrianne R
authors: AR
authors: Wilson-Poe
authors: Vanessa A
authors: VA
authors: Mitchell
authors: Christopher W
authors: CW
authors: Vaughan
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D000613:Aminobutyrates; D002867:Chromones; D003521:Cyclopropanes; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; C120673:benzyloxyaspartate; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D001224:Aspartic Acid; D008734:Methoxyhydroxyphenylglycol; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C121465:6-methyl-2-(phenylethynyl)pyridine; C012729:2-amino-4-phosphonobutyric acid; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol