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Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3513-8. Epub 2005 Feb 16.

Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis.

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  • 1Pharmacology Department, Medical Science Building, Room 4344, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8. philip.seeman@utoronto.ca

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.

PMID:
15716360
[PubMed - indexed for MEDLINE]
PMCID:
PMC548961
Free PMC Article
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