A comparison of M1 and M4 muscarinic receptors in the thalamus from control subjects and subjects with schizophrenia

Abstract

Having shown a decrease in muscarinic M1 receptors in Brodmann’s area (BA) 9 from subjects with schizophrenia we have extended our studies to determine if this receptor is decreased in the thalamus from the same cohort of subjects. Levels of $\text{[}{}^3\text{H}\text{]}$pirenzepine binding to and mRNA encoding for M1 and M4 receptors were measured throughout the thalamus. Levels of M1 and M4 receptor proteins were measured in the mediodorsal nucleus. Two-way ANOVA revealed a variance in $\text{[}{}^3\text{H}\text{]}$pirenzepine binding (F=4.69, d.f. = 1.190, P=0.03), but there was no significant change in radioligand binding in any thalamic region in schizophrenia. Neither levels of mRNA encoding the thalamic M1 or M4 receptor nor levels of M1 or M4 receptor protein in the mediodorsal nucleus differed between the schizophrenic and control subjects. We therefore conclude that the M1 and M4 receptor are not altered in the thalamus from subjects with schizophrenia. These data add weight to the hypothesis that changes in M1 receptors in selective regions of the CNS are associated with the pathology of schizophrenia.