Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 9, Pages 3513-3518Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0409766102
Keywords
addiction; dopamine receptors; gene knockouts; schizophrenia
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Funding
- NIDA NIH HHS [DA12062] Funding Source: Medline
- NIGMS NIH HHS [GM07108-29, T32 GM007108] Funding Source: Medline
- NIMH NIH HHS [MH67497, R01 MH067497] Funding Source: Medline
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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-/-, Dbh(Th/+) (tyrosine hydroxylase), and in rats born by Cesarean-section. The functional state of D2, or the high-affinity state for dopamine (D2(High)), was measured in these supersensitive animal brain striata. Increased levels and higher proportions (40-900%) for D2(High) were found in all these tissues. If many types of brain impairment cause dopamine behavioral supersensitivity and a common increase in D2(High) states, it suggests that there are many pathways to psychosis, any one of which can be disrupted.
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