title: Stimulation of glutamate receptors in the ventral tegmental area is necessary for serotonin-2 receptor-induced increases in mesocortical dopamine release.
abstract: Modulation of dopamine (DA) released by serotonin-2 (5-HT2) receptors has been implicated in the mechanism of action of antipsychotic drugs. The mesocortical DA system has been implicated particularly in the cognitive deficits observed in schizophrenia. Agonism at 5-HT2A receptors in the prefrontal cortex (PFC) is associated with increases in cortical DA release. Evidence indicates that 5-HT2A receptors in the cortex regulate mesocortical DA release through stimulation of a "long-loop" feedback system from the PFC to the ventral tegmental area (VTA) and back. However, a causal role for VTA glutamate in the 5-HT2-induced increases in PFC DA has not been established. The present study does so by measuring 5-HT2 agonist-induced DA release in the cortex after infusions of glutamate antagonists into the VTA of the rat. Infusions of a combination of a N-methyl-d-aspartic acid (NMDA) (AP-5: 2-amino-5-phosphopentanoic acid) and an AMPA/kainate (CNQX: 6-cyano-7-nitroquinoxaline-2,3-dione) receptor antagonist into the VTA blocked the increases in cortical DA produced by administration of the 5-HT2 agonist DOI [(±)-2,5-dimethoxy-4-iodoamphetamine] (2.5mg/kg s.c.). These results demonstrate that stimulation of glutamate receptors in the VTA is necessary for 5-HT2 agonist-induced increases in cortical DA.
authors: Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, OH 44106, USA; Case Western Reserve University, Department of Psychiatry, Cleveland, OH 44106, USA; Case Western Reserve University, Department of Neurosciences, Cleveland, OH 44106, USA. Electronic address: eap6@cwru.edu.
authors: E A
authors: EA
authors: Pehek
authors: Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, OH 44106, USA; Case Western Reserve University, Department of Biology, Cleveland, OH 44106, USA; University of Vermont College of Medicine, Burlington, VT 05405, USA.
authors: A E
authors: AE
authors: Hernan
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000662:Amphetamines; D004298:Dopamine; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D044348:Receptors, Serotonin, 5-HT2; D058826:Serotonin 5-HT2 Receptor Agonists; D014633:Valine; C056639:2-amino-5-phosphopentanoic acid; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine
keywords: AMPA; NMDA; antipsychotic; microdialysis; prefrontal cortex; schizophrenia
references: J Pharmacol Exp Ther. 1989 Oct;251(1):378-87
references: 2552079
references: Cereb Cortex. 2009 Jul;19(7):1678-86
references: 19029064
references: Neuropsychopharmacology. 2006 Feb;31(2):265-77
references: 15999145
references: Front Neurosci. 2010 Aug 13;4:null
references: 20802802
references: J Neurochem. 2002 Jul;82(1):93-100
references: 12091469
references: Pharmacol Ther. 2007 Feb;113(2):296-320
references: 17049611
references: Neuropharmacology. 1998 Jul;37(7):953-5
references: 9776391
references: Arch Gen Psychiatry. 1987 Jul;44(7):660-9
references: 3606332
references: Brain Res. 2001 Jan 5;888(1):51-59
references: 11146051
references: Nat Neurosci. 2003 Sep;6(9):968-73
references: 12897785
references: Neuroscience. 2014 Dec 12;282:60-8
references: 24875175
references: Synapse. 1990;6(1):106-12
references: 1697988
references: Cereb Cortex. 2003 Aug;13(8):870-82
references: 12853374
references: Nat Commun. 2014 Nov 12;5:5390
references: 25388237
references: Neuroscience. 2002;111(1):163-76
references: 11955720
references: Neuropharmacology. 1997 Apr-May;36(4-5):589-99
references: 9225284
references: J Neurosci. 2000 May 15;20(10 ):3864-73
references: 10804226
references: J Neurochem. 1995 Sep;65(3):1407-10
references: 7643120
references: Front Neural Circuits. 2012 Mar 20;6:12
references: 22454619
references: J Gen Physiol. 2012 Jan;139(1):93-6
references: 22200950
references: Pharm Res. 1993 Oct;10(10):1411-9
references: 8272401
references: Synapse. 2000 Jun 1;36(3):205-21
references: 10819900
references: Neuropharmacology. 1999 Feb;38(2):315-7
references: 10218874
references: J Neurosci. 2001 Dec 15;21(24):9856-66
references: 11739593
references: J Neurochem. 1996 Feb;66(2):589-98
references: 8592128
references: Synapse. 1997 Sep;27(1):79-82
references: 9268067
references: J Neurochem. 2005 Dec;95(6):1597-607
references: 16277612
references: J Comp Neurol. 1992 Jun 8;320(2):145-60
references: 1377716
references: Neuroscience. 1991;40(2):399-412
references: 1851255
references: Neuroscience. 2014 Dec 12;282:23-48
references: 24735820