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

Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3513-8. doi: 10.1073/pnas.0409766102. Epub 2005 Feb 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Catechol O-Methyltransferase / genetics
  • Catechol O-Methyltransferase / physiology
  • Corpus Striatum / physiopathology
  • Dopamine / physiology*
  • Dopamine beta-Hydroxylase / genetics
  • Dopamine beta-Hydroxylase / physiology
  • Male
  • Phencyclidine / pharmacology
  • Psychotic Disorders / etiology*
  • Quinpirole / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / physiology*
  • Receptors, Dopamine D4
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / physiology

Substances

  • Drd4 protein, rat
  • Receptors, Dopamine D2
  • Receptors, G-Protein-Coupled
  • Receptors, Dopamine D4
  • Quinpirole
  • Dopamine beta-Hydroxylase
  • Catechol O-Methyltransferase
  • Phencyclidine
  • Dopamine