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March 2000, Volume 5, Number 2, Pages 203-207
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Original Research Article
Muscarinic1 and 2 receptor mRNA in the human caudate-putamen: no change in m1 mRNA in schizophrenia
B Dean1,2, J M Crook1,2, G Pavey1, K Opeskin3 and D L Copolov1

1The Rebecca L Cooper Research Laboratories, The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Australia

2The Department of Pathology, The University of Melbourne, Parkville, Melbourne 3052, Australia

3The Victorian Institute of Forensic Medicine, Monash University, Southbank, Victoria 3006, Australia

Correspondence to: Dr B Dean, The Rebecca Cooper Research Laboratories, The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Australia. E-mail: bri@mhri.edu.au

Abstract

Studies using tissue obtained at autopsy suggest that changes in cholinergic neurons could be important in the pathology of schizophrenia.1234 We have previously reported a decrease in [3H]pirenzepine binding5 and [3H]AF-DX 384 binding6 to caudate-putamen (CP) from subjects who had schizophrenia. Under the conditions chosen, [3H]pirenzepine would predominately bind to muscarinic1 (M1) and muscarinic4 (M4) receptors,7whereas [3H]AF-DX 384 would mainly bind to muscarinic2 (M2) and M4 receptors.8 Given the relative concentrations of M1, M2 and M4 receptors in the human CP and the magnitude of the decreases in radioligand binding in schizophrenia, our results most likely reflected a change in the density of M1 and M2 receptors in the CP from the schizophrenic subjects. In situ hybridisation has now been used to determine levels of m1 and m2 mRNA in CP from 14 schizophrenic and 16 control subjects previously used for radioligand binding. m2 mRNA in the CP from the schizophrenic and control subjects was below the sensitivity of in situhybridisation. There was no difference in the levels of m1 mRNA in CP from schizophrenic and control subjects (mean ± SEM: 103 ± 16 vs106 ± 17 fmol [35S]oligonucleotide probe g-1estimated tissue equivalents, P = 0.91). In conclusion, data from our radioligand binding studies show decreases in [3H]pirenzepine binding that are likely to reflect a decrease in the density of M1 receptors in CP from schizophrenic subjects. Our data in this study show the absence of a concomitant change in mRNA coding for that receptor. Molecular Psychiatry (2000) 5, 203-207.

Keywords

schizophrenia; muscarinic receptors; postmortem; caudate-putamen; in situ hybridisation

Received 5 March 1999; revised 7 September 1999; accepted 7 September 1999
March 2000, Volume 5, Number 2, Pages 203-207
Table of contents    Previous  Abstract  Next   Full text  PDF
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