Abstract
To test the hypothesis that muscarinic receptors are involved in the pathology of schizophrenia, we measured muscarinic1 (M1R) and muscarinic4(M4R) protein and mRNA as well as [3H]pirenzepine binding in Brodmann's areas (BA) 9 and 40 obtained postmortem from 20 schizophrenic and 20 age/sex-matched control subjects. There was a significant decrease in [3H]pirenzepine binding to BA 9 (mean ± SEM: 151 ± 15 vs 195 ± 10 fmol mg−1 ETE; P< 0.02), but not BA 40 (143 ± 13 vs 166 ± 11 fmol mg−1 ETE), from subjects with schizophrenia. The level of M1R protein (0.11 ± 0.007 vs 0.15 ± 0.008 OD; P < 0.01), but not M4R protein, was decreased in BA9 from schizophrenic subjects with neither receptor protein being altered in BA 40. The level of M1R mRNA was decreased in BA 9 (30 ± 7.0 vs 79 ± 14 dpm × 103 mg−1ETE, P < 0.01) and BA 40 (28 ± 5.9 vs 99 ± 14, P < 0.01) with schizophrenia but M4R mRNA was only decreased in BA 40 (48 ± 6.6 vs 89 ± 9.9, P < 0.005). These data suggest that the M1R, at least in the dorsolateral prefrontal cortex, may have a role in the pathology of schizophrenia.
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Acknowledgements
The authors would like to acknowledge Dr Ken Opeskin and the Staff at the Victorian Institute of Forensic Medicine for their assistance with the collection of tissue, Professor Nicholas Keks and Ms Christine Hill for providing diagnostic confirmation and Mr Geoffrey Pavey for his efforts in curating the tissue collection at the Mental Health Research Institute. This work was financed in part by Grants-in-Aid from the Rebecca L Cooper Research Laboratories, the Stanley Foundation and the Wood's Family Trust and NH&MRC Project (grant 209046).
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Dean, B., McLeod, M., Keriakous, D. et al. Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia. Mol Psychiatry 7, 1083–1091 (2002). https://doi.org/10.1038/sj.mp.4001199
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DOI: https://doi.org/10.1038/sj.mp.4001199
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