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A glutamatergic deficiency model of schizophrenia

Published online by Cambridge University Press:  06 August 2018

A. Carlsson ,
L. O. Hansson ,
N. Waters  and
M. L. Carlsson
A. Carlsson*
Affiliation:
Department of Pharmacology, University of Goteborg, Sweden
L. O. Hansson
Affiliation:
Department of Pharmacology, University of Goteborg, Sweden
N. Waters
Affiliation:
Department of Pharmacology, University of Goteborg, Sweden
M. L. Carlsson
Affiliation:
Department of Pharmacology, University of Goteborg, Sweden
*
Correspondence: Dr A. Carlsson, Department of Pharmacology, University of Göteborg, Box 431, 40530 Goteborg, Sweden
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Abstract

Although the presence of hyperdopaminergia has been demonstrated in the brains of people with schizophrenia, at least in some circumstances, other neurotransmitters are important in this disorder, and a glutamatergic deficiency model of schizophrenia is proposed. It is suggested that the amount of sensory input allowed to reach the cerebral cortex is restricted by an inhibitory effect of the striatal complexes on the thalamus, thereby protecting it from being overwhelmed. Several strands of evidence are presented to support the concept that a weakened glutamatergic tone increases the risk of sensory overload and of exaggerated responses in the monoaminergic systems that could result in psychosis.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 174 , Issue S37: Focus on schizophrenia , February 1999 , pp. 2 - 6
Copyright
Copyright © The Royal College of Psychiatrists, 1999 

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References

Andén, N.-E., Butcher, S. G., Corrodi, H., et al (1970) Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. European Journal of Pharmacology, 11, 303–314.Google Scholar
Breier, A., Sue, T.-R., Saunders, R., et al (1997) Schizophrenia is associated with elevated amphetamine-induced synaptic concentrations: evidence from a novel positron emission tomography method. Proceedings of the National Academy of Sciences of the United States of America, 94, 2569–2574.Google Scholar
Carlsson, A. (1988) The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology, 1, 179–203.Google Scholar
Carlsson, A. & Lindqvist, M. (1963) Effect of chlorpromazine or haloperidol on the formation of 3-methoxytyramine and normetanephrine on mouse brain. Acta Pharmacologica et Toxicologica, 20, 140–144.CrossRefGoogle ScholarPubMed
Carlsson, A., Hansson, L. O., Waters, N., et al (1997) Neurotransmitter aberrations in schizophrenia: new perspectives and therapeutic applications. Life Sciences, 61, 75–94.CrossRefGoogle Scholar
Carlsson, M. L. (1995) The selective 5-HT2A receptor antagonist MDL 100,907 counteracts the psychomotor stimulation ensuing manipulations with monoaminergic, glutamatergic or muscarinic neurotransmission in the mouse: implications for psychosis. Journal of Neural Transmission, 100, 225–237.Google Scholar
Carlsson, M. L. & Carlsson, A. (1989) The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice. Journal of Neural Transmission, 75, 221–226.CrossRefGoogle ScholarPubMed
Creese, I., Burt, D. R. & Snyder, S. (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science, 192, 481–483.Google Scholar
Dao-Castellana, M.-H., Paillere-Martinot, M.-L., Hantraye, P., et al (1997) Presynaptic dopaminergic function in the striatum of schizophrenic patients. Schizophrenia Research, 23, 167–174.CrossRefGoogle ScholarPubMed
Hietala, J., Syvalahti, E.,Vuorio, K., et al (1995) Presynaptic dopamine function in striatum of neuroleptic-na'ive schizophrenic patients. Lancet, 346, 1130–1131.Google Scholar
Laruelle, M., Abi-Dargham, A., Gil, R., et al (1996) Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proceedings of the National Academy of Sciences of the United States of America, 18, 198.Google Scholar
Martin, P., Waters, N. R., Waters, S. E., et al (1997) MK-801-induced hyperlocomotion: differential effects of MDL 100,907, SDZ PSD 958 and raclopride. European Journal of Pharmacology, 335, 107–116.Google Scholar
Miller, D. W. & Abercrombie, E. (1996) Effects of MK-801 on spontaneous and amphetamine-stimulated dopamine release in striatum measured with in vivo microdialysis in awake rats. Brain Research Bulletin, 40, 57–62.CrossRefGoogle ScholarPubMed
Nyback, H. & Sedvall, G. (1970) Further studies on the accumulation and disappearance of catecholamines formed from tyrosine-14-C in mouse brain. European Journal of Pharmacology, 10, 193–205.Google Scholar
Schmidt, C., Sorensen, S. M., Kehne, J. H., et al (1995) The role of 5-HT2A receptors in antipsychotic activity. Life Sciences, 56, 2209–2222.Google Scholar
Seeman, P., Lee, T., Chau-Wong, M., et al (1976) Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature, 261, 717–719.Google Scholar
Stille, G. (1976) Neurophysiological correlates to antipsychotic effects of drug. In Antipsychotic Drugs: Pharmacodynamics and Pharmacokinetics (eds Sedvall, F., Uvnas, B. & Zotterman, Y.), pp. 51–62. Oxford: Pergamon Press.Google Scholar
Svensson, A. & Carlsson, M. L. (1992) Injection of the competitive NMDA receptor antagonist AP-5 into the nucleus accumbens of monoamine-depleted mice induces pronounced locomotor stimulation. Neuropharmacology, 31, 513–518.Google Scholar
Tamminga, C. A. Crayton, J. C. & Chase, T. N. (1978) Muscimol: GABA agonist therapy in schizophrenia. American Journal of Psychiatry, 135, 746–748.Google Scholar
Waters, N., Carlsson, A. & Hansson, L. (1994) An animal model of schizophrenia based on multivariate analysis of monoaminergic biochemistry and behaviour. Society of Neuroscience Abstracts, 20, 1, 825.Google Scholar
Waters, N., Carlsson, A. & Hansson, L. (1995) Evaluation of drug effects in a multivariate animal model of schizophrenia. Society of Neuroscience Abstracts, 21, I, 825.Google Scholar
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