Altered hippocampal muscarinic M4, but not M1, receptor expression from subjects with schizophrenia

Background: Having shown a decrease in [H-3]pirenzepine binding in the hippocampus from subjects with schizophrenia, we wished to determine whether such a change in radioligand binding was associated with changes in hippocampal mRNA for the muscarinic(1) (M1) and muscarinc(4) (M4) receptors in tissue from different cohorts of subjects. Method: The [H-3]pirenzepine binding using autoradiography and in situ hybridization with oligonucleotides specific for muscarinic M1 and M4 receptors were completed using hippocampal tissue obtained postmortem from 20 control subjects and 20 subjects with schizophrenia. Results: The [H-3]pirenzepine binding was decreased in the dentate gyrus (p <.05), CA3 (p <.01), CA2 (p <.05), and CA1 (P <.01) regions of the hippocampus from subjects with schizophrenia. Levels of M4 mRNA varied with the diagnosis of schizophrenia (p = .01), but significant region-specific changes were not apparent. Changes in levels of mRNA for the muscarinic M1 receptor were not detected with diagnosis. Conclusions: This study suggests that decreases in hippocampal [H-3]pirenzepine binding in subjects with schizophrenia are most likely associated with widespread changes in expression levels of the M4 receptor. These data further implicate the hippocampal formation in the pathology of schizophrenia.