title: Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis.
abstract: Dopamine supersensitivity occurs in schizophrenia and other psychoses, and after hippocampal lesions, antipsychotics, ethanol, amphetamine, phencyclidine, gene knockouts of Dbh (dopamine beta-hydroxylase), Drd4 receptors, Gprk6 (G protein-coupled receptor kinase 6), Comt (catechol-O-methyltransferase), or Th-/-, DbhTh/+ (tyrosine hydroxylase), and in rats born by Cesarean-section. The functional state of D2, or the high-affinity state for dopamine (D2High), was measured in these supersensitive animal brain striata. Increased levels and higher proportions (40-900%) for D2High were found in all these tissues. If many types of brain impairment cause dopamine behavioral supersensitivity and a common increase in D2High states, it suggests that there are many pathways to psychosis, any one of which can be disrupted.
authors.affiliation: Pharmacology Department, Medical Science Building, Room 4344, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8. philip.seeman@utoronto.ca
authors.forename: Philip
authors.initials: P
authors.lastname: Seeman
authors.forename: David
authors.initials: D
authors.lastname: Weinshenker
authors.forename: Remi
authors.initials: R
authors.lastname: Quirion
authors.forename: Lalit K
authors.initials: LK
authors.lastname: Srivastava
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Bhardwaj
authors.forename: David K
authors.initials: DK
authors.lastname: Grandy
authors.forename: Richard T
authors.initials: RT
authors.lastname: Premont
authors.forename: Tatyana D
authors.initials: TD
authors.lastname: Sotnikova
authors.forename: Patricia
authors.initials: P
authors.lastname: Boksa
authors.forename: Mufida
authors.initials: M
authors.lastname: El-Ghundi
authors.forename: Brian F
authors.initials: BF
authors.lastname: O'dowd
authors.forename: Susan R
authors.initials: SR
authors.lastname: George
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Perreault
authors.forename: Pekka T
authors.initials: PT
authors.lastname: Männistö
authors.forename: Siobhan
authors.initials: S
authors.lastname: Robinson
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
authors.forename: Teresa
authors.initials: T
authors.lastname: Tallerico
mesh_terms: D000818:Animals; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000502:physiology; D003342:Corpus Striatum / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000502:physiology; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology; D011618:Psychotic Disorders / Q000209:etiology*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000502:physiology*; D050638:Receptors, Dopamine D4; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology
chemical_list: C493601:Drd4 protein, rat; D017448:Receptors, Dopamine D2; D043562:Receptors, G-Protein-Coupled; D050638:Receptors, Dopamine D4; D019257:Quinpirole; D004299:Dopamine beta-Hydroxylase; D002394:Catechol O-Methyltransferase; D010622:Phencyclidine; D004298:Dopamine
references.citation: Endocrinology. 1985 Aug;117(2):690-7
references.pmid: 4017954
references.citation: Neuron. 2003 Apr 24;38(2):291-303
references.pmid: 12718862
references.citation: Mol Psychiatry. 2003 Nov;8(11):911-5
references.pmid: 14593428
references.citation: Psychopharmacology (Berl). 2004 Feb;172(1):1-10
references.pmid: 14574438
references.citation: Can J Psychiatry. 2002 Feb;47(1):27-38
references.pmid: 11873706
references.citation: Br J Psychiatry. 2004 Sep;185:196-204
references.pmid: 15339823
references.citation: Brain Res. 2003 Aug 8;980(2):266-74
references.pmid: 12867267
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13873-7
references.pmid: 12370425
references.citation: J Neurochem. 1984 Nov;43(5):1310-8
references.pmid: 6208330
references.citation: J Pharmacol Exp Ther. 2003 May;305(2):625-31
references.pmid: 12606608
references.citation: Neuroreport. 1997 Jul 28;8(11):2523-7
references.pmid: 9261820
references.citation: J Neurosci. 2000 Jun 15;20(12):4405-13
references.pmid: 10844009
references.citation: Synapse. 2004 May;52(2):77-83
references.pmid: 15034913
references.citation: Neuroscience. 2003;122(3):669-76
references.pmid: 14622910
references.citation: Am J Hum Genet. 2003 Jul;73(1):34-48
references.pmid: 12802786
references.citation: Cell. 1997 Sep 19;90(6):991-1001
references.pmid: 9323127
references.citation: Addiction. 2000 Aug;95 Suppl 2:S91-117
references.pmid: 11002906
references.citation: Brain Res. 2001 Feb 16;892(1):86-93
references.pmid: 11172752
references.citation: Cell. 1995 Dec 29;83(7):1197-209
references.pmid: 8548806
references.citation: BMC Neurosci. 2001;2:4
references.pmid: 11316464
references.citation: Exp Neurol. 2002 Jun;175(2):388-97
references.pmid: 12061868
references.citation: Psychiatry Res. 1995 Aug 8;61(2):67-83
references.pmid: 7480390
references.citation: Synapse. 2003 Sep 15;49(4):209-15
references.pmid: 12827639
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9991-6
references.pmid: 9707588
references.citation: Proc Natl Acad Sci U S A. 1975 Nov;72(11):4376-80
references.pmid: 1060115
references.citation: Psychopharmacology (Berl). 1982;76(2):182-7
references.pmid: 6805029
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13329-34
references.pmid: 15317940
references.citation: Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8104-9
references.pmid: 10884434
references.citation: Synapse. 2002 Dec 15;46(4):235-9
references.pmid: 12373738