Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis.
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.
Seeman
Philip
P
Pharmacology Department, Medical Science Building, Room 4344, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8. philip.seeman@utoronto.ca
Weinshenker
David
D
Quirion
Remi
R
Srivastava
Lalit K
LK
Bhardwaj
Sanjeev K
SK
Grandy
David K
DK
Premont
Richard T
RT
Sotnikova
Tatyana D
TD
Boksa
Patricia
P
El-Ghundi
Mufida
M
O'dowd
Brian F
BF
George
Susan R
SR
Perreault
Melissa L
ML
Männistö
Pekka T
PT
Robinson
Siobhan
S
Palmiter
Richard D
RD
Tallerico
Teresa
T
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
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
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