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

Abstract

Studies using tissue obtained at autopsy suggest that changes in cholinergic neurons could be important in the pathology of schizophrenia.^{1, 2, 3, 4} 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.