Muscarinic1 and 2 receptor mRNA in the human caudate-putamen:: no change in m1 mRNA in schizophrenia

Studies using tissue obtained at autopsy suggest that changes in cholinergic neurons could be important in the pathology of schizophrenia.(1-4) We have previously reported a decrease in [H-3]pirenzepine binding(5) and [H-3]AF-DX 384 binding(6) to caudate-putamen (CP) from subjects who had schizophrenia. Under the conditions chosen, [3H]pirenzepine would predominately bind to muscarinic(1) (M-1) and muscarinic(4) (M-4) receptors,(7) whereas [H-3]AF-DX 384 would mainly bind to muscarinic(2) (M-2) and M-4 receptors.(8) Given the relative concentrations of M-1, M-2 and M-4 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 M-1 and M-2 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 situ hybridisation. There was no difference in the levels of mi mRNA in CP from schizophrenic and control subjects (mean +/- SEM: 103 +/- 16 vs 106 +/- 17 fmol [S-35]oligonucleotide probe g(-1) estimated tissue equivalents, P = 0.91). In conclusion, data from our radioligand binding studies show decreases in [H-3]pirenzepine binding that are likely to reflect a decrease in the density of M-1 receptors in CP from schizophrenic subjects. Our data in this study show the absence of a concomitant change in mRNA coding for that receptor.