M2/M4 muscarinic receptor binding in the anterior cingulate cortex in schizophrenia and mood disorders.
We have previously shown a decrease in [(3)H]pirenzepine binding to M1/M4 muscarinic receptors in the anterior cingulate cortex in schizophrenia but not in major depression or bipolar disorder. The present study aimed to extend these findings by examining the binding of [(3)H]AF-DX 384 to M2/M4 receptors in the same cohort of subjects. Using quantitative autoradiography we measured [(3)H]AF-DX 384 binding in the anterior cingulate cortex of 15 schizophrenia, 15 bipolar, 15 major depression and 15 control cases. Post-mortem tissue was obtained from the Stanley Foundation Brain Bank. [(3)H]AF-DX 384 binding had a homogenous distribution amongst the layers of the anterior cingulate cortex, was higher in males than in females and declined with prolonged storage of tissue. An inverse correlation between [(3)H]AF-DX384 binding and age of onset of the disease was observed in the schizophrenia group suggesting that the earlier the age at onset the higher the binding was. In the depression group, there was a significant effect of gender on [(3)H]AF-DX 384 binding with females having lower binding in comparison to males. In the bipolar group, there was a significant inverse correlation between antipsychotic medication and [(3)H]AF-DX 384 binding, suggesting that the higher the dose of medication the lower the binding was. No differences in [(3)H]AF-DX 384 binding were seen between the four groups. The present results provide no evidence of M2/M4 receptor alterations in the anterior cingulate cortex in schizophrenia and affective disorders and extend the body of evidence implicating cortical M1 but not M2 involvement in the pathology and pharmacotherapy of schizophrenia.
Zavitsanou
Katerina
K
Radiopharmaceuticals R&D, Australian Nuclear Science and Technology Organisation (ANSTO), PMB 1, Menai, Sydney, NSW 2234, Australia. kza@ansto.gov.au
Katsifis
Andrew
A
Yu
Yinghua
Y
Huang
Xu Feng
XF
D000328:Adult; D017668:Age of Onset; D000704:Analysis of Variance; D001345:Autoradiography; D001931:Brain Mapping; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000378:metabolism*; D009929:Organ Size; D010276:Parasympatholytics / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011180:Postmortem Changes; D011485:Protein Binding / Q000187:drug effects; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D043588:Receptor, Muscarinic M4 / Q000378:metabolism*; D012044:Regression Analysis; D012559:Schizophrenia / Q000378:metabolism*; D012737:Sex Factors; D014316:Tritium / Q000494:pharmacology
D010276:Parasympatholytics; D043585:Receptor, Muscarinic M2; D043588:Receptor, Muscarinic M4; D014316:Tritium; C065959:AFDX 384; D010890:Pirenzepine