Background:
Changes in muscarinic receptors are widespread in the brains of subjects with schizophrenia, implicating them in the pathology of the disorder (Hyde & Crook Chem Neuroanat 2001, 22 53–63). A previous study showed decreased levels of mRNA for the muscarinic M1 receptor in Brodmann's area (BA) 6 from subjects with schizophrenia (Mancama et al. Am J Med Genet B Neuropsychiatr Genet 2003, 119 2–6). The purpose of our study was to further investigate this finding.
Methods:
Using in situ radioligand binding and autoradiography, the density of [3H]pirenzepine binding was determined in BA 6 obtained postmortem from 20 subjects with schizophrenia and 20 subjects with no psychiatric history (controls).
Results:
[3H]Pirenzepine binding was differentially distributed in the cortical gray matter (inner layer = gray1; outer layer = gray2). [3H]Pirenzepine binding was significantly lower in tissue from subjects with schizophrenia than in that from control subjects in both gray1 (mean ± SEM, 74.56 ± 10.67 vs. 118.80 ± 5.47 fmol//mgETE, P < 0.01) and gray2 layers (102.90 ± 14.09 vs. 152.90 ± 8.04, P < 0.01). Furthermore, [3H]pirenzepine binding was significantly different between layers in control subject tissue (gray1, 118.80 ± 5.47; gray2, 152.90 ± 8.04; P < 0.05), but not in that from subjects with schizophrenia (gray1, 74.56 ± 10.67; gray2 102.90 ± 14.09; P > 0.05).
Conclusion:
These results support previous findings that levels of M1 and/or M4 muscarinic receptors are significantly altered in cortical regions from subjects with schizophrenia, extending the regions affected to include BA6.
