The Dopamine Hypothesis of Schizophrenia: New Aspects

  • Arvid Carlsson
Part of the Advances in Behavioral Biology book series (ABBI, volume 53)


In spite of its proven heuristic value, the dopamine hypothesis of schizophrenia is now yielding to a multifactorial view, where the other monoamines as well as glutamate and GABA are included, with a focus on neurotransmitter interactions in complex neurocircuits. The primary lesion(s) in schizophrenia do not necessarily involve any of these neurotransmitters directly but could deal with a more general defect, such as a faulty connectivity of developmental origin. Nevertheless, a precise identification of neurotransmitter aberrations in schizophrenia will probably provide clues for a better understanding of the disease and for the development of new treatment and prevention strategies.


Positron Emission Tomography Schizophrenic Patient Dopaminergic Function Antipsychotic Action Schizophrenia Research 
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  1. 1.
    Bunney BG, Potkin SP, Bunney WE Jr. 1995. New morphological and neuropathological findings in schizophrenia: a neurodevelopmental perspective. Clin. Neurosci. 3:81–88PubMedGoogle Scholar
  2. 2.
    Carlsson A. 1995. The dopamine theory revisited. In Schizophrenia, eds. SR Hirsch, DR Weinberger, pp. 379–400. Oxford: Blackwell ScienceGoogle Scholar
  3. 3.
    Hietala J, Syvälahti E, Vuorio K, Någren K, Lehikoinen P, Ruotsalalainen U et al. 1994. Striatal D2- dopamine receptor characteristics in neuroleptic-naive schizophrenic patients studied with positron emission tomography. Arch. Gen. Psychiatry 51:116–123PubMedCrossRefGoogle Scholar
  4. 4.
    Dao-Costellana M-H, Paillère-Martinot M-L, Hantraye P, Attar-Lévy D, Rémy P, Crouzel C et al. 1997. Presynaptic dopaminergic function in the striatum of schizophrenic patients. Schizophrenia Research 23:167–174CrossRefGoogle Scholar
  5. 5.
    Lindström LH, Gefvert O, Hagberg G, Hagström P, Lundberg T, Bergström P et al. 1997. Increased synthesis of dopamine in prefrontal cortex and striatum in drug-naive schizophrenic patients studied by use of C11-labelled 1-DOPA and positron emission tomography (PET). Abstract, 36th Annual ACNP Meelting, December 8–12, 1997, p. 290Google Scholar
  6. 6.
    Lamelle M, Abi -Dargham A, van Dyck CH, Gil R, D’Souza CD, Erdos J, McCance E et al. 1996. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug- free schizophrenic subjects. Proc. Natl. Acad. Sci. USA. 20, 93(17): 9235–40Google Scholar
  7. 7.
    Breier A, Su T-P, Saunders R, Carson RE, Kolachana BS, de Bartolomeis A et al. 1997. Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: Evidence from a novel positron emission tomography method. Proc. Natl. Acad. Sci. USA 94:2569–2574PubMedCrossRefGoogle Scholar
  8. 8.
    Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Lamelle M et al. 1998. Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am. J. Psychiatry 155: 761–767PubMedGoogle Scholar
  9. 9.
    Lamelle M. 2000. Imaging dopamine dysregulation in schizophrenia: Implication for treatment. Presented at Workshop Schizophrenia: Pathological Bases and Mechanisms of Antipsychotic action, ChicagoGoogle Scholar
  10. 10.
    Lahti AC, Weiler MA, Corey PK, Lahti RA, Carlsson A, Tamminga CA. 1998. Antipsychotic properties of the partial dopamine agonist (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine (preclamol) in schizophrenia. Biol. Psychiat. 43:2–11PubMedCrossRefGoogle Scholar
  11. 11.
    Svensson K, Hjorth S, Clark D, Carlsson A, Wikström H, Andersson B, et al. 1986. (+)-UH 232 and (+)-UH 242: Novel stereoselective DA receptor antagonists with preferential action on autoreceptors. J.Neural Transm. 65:1–27PubMedCrossRefGoogle Scholar
  12. 12.
    Sonesson C, Lin C-H, Hansson L, Waters N, Svensson K, Carlsson A et al. 1994. Substituted (S)- phenylpiperidines and rigid congeners as preferential dopamine autoreceptor antagonists: Synthesis and structure-activity relationships. J. Med. Chem. 37:2735–2753PubMedCrossRefGoogle Scholar
  13. 13.
    Hansson LO, Waters N, Holm S, Sonesson C.1995. On the quantitative structure-activity relationships of mem-substituted (S)-phenylpiperidines, a class of preferential dopamine D2 autoreceptor ligands. Modeling of dopamine synthesis and release in vivo by means of partial least squares regression. J.Med. Chem. 38:3121–3131PubMedCrossRefGoogle Scholar
  14. 14.
    Ekesbo A, Andrén PE, Gunne LM, Tedroff J. 1997. (-)-OSU6162 inhibits levodopa-induced dyskinesias in a monkey model of Parkinson’s disease. Neuroreport 8:2567–2570PubMedCrossRefGoogle Scholar
  15. 15.
    Tedroff J, Ekesbo A, Sonesson C, Waters N, Carlsson A. 1999. Long-lasting improvement following (-)- OSU6162 in a patient with Huntington’s disease. Neurology 53:1605–1606PubMedCrossRefGoogle Scholar
  16. 16.
    Gefvert O, Lindström LH, Dahlbäck O, Sonesson C, Waters N et al. 2000. (-)-OSU6162 induces a rapid onset of antipsychotic effect after a single dose. A double-blind study. Presented at Scand. Soc. Psychopharmacol., 41st meeting. Nordic J. Psychiat. 54/2:93–94Google Scholar
  17. 17.
    Ågren H, Reibring L, Hartvig P, Tedroff J, Bjurling P, Hornfeldt K et al. 1991. Low brain uptake of L- [11C]5-hydroxytryptophan in major depression: a positron emission tomography study on patients and healthy volunteers. Acta Psychiatr. Scand. 83:449–455PubMedCrossRefGoogle Scholar
  18. 18.
    Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmüller. 1980. Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci. Lett. 20:379–382PubMedCrossRefGoogle Scholar
  19. 19.
    Garland Bunney B, Bunney WE, Carlsson A. 1995. Schizophrenia and glutamate. In Psychopharmacology: The Fourth Generation of Progress, eds. FE Bloom, DJ Kupfer, pp. 1203–1214, New York: Raven PressGoogle Scholar
  20. 20.
    Lodge D.1989. Modulation of N-methylaspartate receptor channel complexes. Drugs of Today 25:395–411Google Scholar
  21. 21.
    Carlsson A, Lindqvist M.1963. Effect of chlorpromazine or haloperidol on the formation of 3- methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol. (Kbh.) 20:140–144CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Arvid Carlsson
    • 1
  1. 1.Department of Physiology and PharmacologyUniversity of GöteborgGöteborgSweden

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