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

Philip Seeman, David Weinshenker, Remi Quirion, Lalit K. Srivastava, Sanjeev K. Bhardwaj, David K. Grandy, Richard T. Premont, Tatyana D. Sotnikova, Patricia Boksa, Mufida El-Ghundi, Brian F. O'Dowd, Susan R. George, Melissa L. Perreault, Pekka T. Männistö, Siobhan Robinson, Richard D. Palmiter, Teresa Tallerico

    Research output: Contribution to journalArticle

    254 Scopus citations

    Abstract

    Dopamine supersensitivity occurs in schizophrenia and other psychoses, and after hippocampal lesions, antipsychotics, ethanol, amphetamine, phencyclidine, gene knockouts of Dbh (dopamine β-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.

    Original languageEnglish (US)
    Pages (from-to)3513-3518
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume102
    Issue number9
    DOIs
    StatePublished - Mar 1 2005

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    Keywords

    • Addiction
    • Dopamine receptors
    • Gene knockouts
    • Schizophrenia

    ASJC Scopus subject areas

    • General

    Cite this

    Seeman, P., Weinshenker, D., Quirion, R., Srivastava, L. K., Bhardwaj, S. K., Grandy, D. K., Premont, R. T., Sotnikova, T. D., Boksa, P., El-Ghundi, M., O'Dowd, B. F., George, S. R., Perreault, M. L., Männistö, P. T., Robinson, S., Palmiter, R. D., & Tallerico, T. (2005). Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis. Proceedings of the National Academy of Sciences of the United States of America, 102(9), 3513-3518. https://doi.org/10.1073/pnas.0409766102