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Decreased M1 muscarinic receptor density in rat amphetamine model of schizophrenia is normalized by clozapine, but not haloperidol

  • Biological Psychiatry - Original Article
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Abstract

There is increasing evidence supporting the involvement of the muscarinic–cholinergic system in schizophrenia. We examined the M1 muscarinic receptor density and mRNA expression in brains of a rat amphetamine model of schizophrenia. We also assessed the effect of the model and chronic treatment with haloperidol and clozapine on brain M1 receptor density and gene expression. A significant decrease of about 20% in the density of M1 receptor was detected in the cortex and in the striatum of amphetamine model rats. A significant increase of 33% in the density of the M1 receptor was found in the cortex and striatum of rats treated chronically with clozapine (0.5 mg/kg), but not with haloperidol (25 mg/kg). Chronic clozapine, but not haloperidol, normalized the decrease in M1 receptors observed in amphetamine model rats, in both cortex and striatum. Regulation of the M1 receptor may occur in a post-transcriptional phase. Our findings suggest involvement of both dopaminergic and cholinergic–muscarinic systems in the pathophysiology and pharmacotherapy of schizophrenia.

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Acknowledgments

We would like to thank Dr. Shifra Ben Dor from the Department of Biological Services in the Weizmann Institute of Science, Rehovot, Israel, for her assistance in the bioinformatic aspects of this study.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Adi Malkoff, Abraham Weizman & Moshe Rehavi

  2. Research Unit, Geha Mental Health Center, Petah Tikva, Israel

    Abraham Weizman

  3. Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Beilinson Campus, Petah Tikva, Israel

    Abraham Weizman

  4. Elton Molecular Neuroendocrinology Laboratory, Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Illana Gozes

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  1. Adi Malkoff
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  2. Abraham Weizman
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  4. Moshe Rehavi
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Correspondence to Moshe Rehavi.

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Malkoff, A., Weizman, A., Gozes, I. et al. Decreased M1 muscarinic receptor density in rat amphetamine model of schizophrenia is normalized by clozapine, but not haloperidol. J Neural Transm 115, 1563–1571 (2008). https://doi.org/10.1007/s00702-008-0122-8

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  • DOI: https://doi.org/10.1007/s00702-008-0122-8

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