Decreased muscarinic receptor binding in the frontal cortex of bipolar disorder and major depressive disorder subjects

Abstract

Background-Dysfunction of the cholinergic muscarinic receptors has been implicated in the pathology of bipolar disorder and major depressive disorder. However, there is conflicting evidence regarding the association between individual muscarinic receptors and the two disorders.Methods-We used the muscarinic receptor selective radioligands [ 3 H]pirenzepine, [ 3 H] AFDX-384 and [ 3 H]4-DAMP to measure the levels of muscarinic 1 (CHRM1) and muscarinic 4 (CHRM4) receptors, muscarinic 2 (CHRM2) and muscarinic 4 (CHRM4) receptors and muscarinic 3 (CHRM3) receptor, respectively. Radioligand binding was measured in Brodmann's area (BA) 10 of the rostral prefrontal cortex, BA 46 of the dorsolateral prefrontal cortex and BA 40 of the parietal cortex in the post-mortem CNS from subjects with bipolar disorder or major depressive disorder and control subjects. Limitations-9 bipolar disorder, 9 major depressive disorder and 19 control subjects were used in the study. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusion-Our data is consistent with previously published data implicating a role for CHRM2 receptors in the pathology of bipolar and major depressive disorder. The demonstration of a novel association between decreased CHRM3 receptor expression and bipolar disorder suggests bipolar and major depressive disorder differ in the underlying nature of their cholinergic dysfunction. Results-[ NIH Public Access

Anxiolytic effects of muscarinic acetylcholine receptors agonist oxotremorine in chronically stressed rats and related changes in BDNF and FGF2 levels in the hippocampus and prefrontal cortex

“…Although here we did not examine the receptor subtype involved in the Oxo anxiolytic effect, several reports may give suggestions on antidepressant role of M1 receptor, which has been found throughout the brain with the highest concentrations in cerebral cortex and hippocampus (Hohmann et al 1995;Levey et al 1995). Previous works have shown that disturbances in the cholinergic activity may be associated to neurobiology of depression (Janowsky et al 1972), and muscarinic receptors have been found downregulated in the prefrontal cortex of depressed patients (Gibbons et al 2009), or upregulated in the hippocampus following mood stabilizers like lithium treatment (Marinho et al 1998). Recent studies have identified an activity-dependent long-term depression in deep layers of the rat medial prefrontal cortex mediated by the M1 receptor, which may be relevant for neurological disorders (Caruana et al 2011).…”

M1and M2Muscarinic Receptor Subtypes Regulate Antidepressant-Like Effects of the Rapidly Acting Antidepressant Scopolamine

“…Using radiolabels for M 1 -M 4 , Gibbons et al (2009) evaluated receptor density changes in the postmortem frontal cortex of patients with MDD or bipolar disorder (BD). Both M 2 and M 3 binding sites were downregulated in MDD but only M 2 in BD.…”

Muscarinic Receptors: Their Roles in Disorders of the Central Nervous System and Potential as Therapeutic Targets

“…More integrative approaches, determining expression at the levels of radioligand binding, mRNA, and protein, lead to the discovery that in the cortex the reduced binding density was due to lower levels of the M1 receptor [44], while in the hippocampus it was the M4 receptor that was expressed at a lower level [45]. Of particular note are the findings that in psychiatric disorders: (1) the decrease in the M1 receptor is specific to schizophrenia [42,46] and (2) changes in M2 and M3 receptors appear to be limited to subcortical regions [47,48].…”