title: Widespread decreases in cortical muscarinic receptors in a subset of people with schizophrenia.
abstract: These studies were undertaken to investigate the selectivity of cortical muscarinic receptor radioligand binding in muscarinic M(1) and M(4) receptor knockout mice and to determine whether a marked decrease in [(3)H]pirenzepine binding in Brodmann's area (BA) 9 from a subset of people with schizophrenia was predictive of decreased muscarinic receptors in other central nervous system (CNS) regions. Our data show that, under the conditions used, [(3)H]pirenzepine binding was highly selective for the muscarinic M(1) receptor whereas both [(3)H]AF-DX 386 and [(3)H]4DAMP had less discriminatory power. In addition, the data suggest that a marked decrease in [(3)H]pirenzepine binding in BA 9 from a subset of people with schizophrenia is predictive of decreases in muscarinic receptors in other CNS regions. However, there were some region-specific decreases in muscarinic receptors in tissue from people with schizophrenia who were outside this subset. These data add to a growing body of evidence suggesting there are widespread decreases in muscarinic receptors in the CNS of some subjects with schizophrenia, as demonstrated by neuroimaging. Our data have implications for understanding the potential clinical utility of drugs directed at the orthosteric and allosteric sites of muscarinic receptors to treat schizophrenia.
authors.affiliation: Rebecca L. Cooper Research Laboratories, Mental Health Research Institute, Parkville, VIC, Australia.
authors.forename: Andrew Stuart
authors.initials: AS
authors.lastname: Gibbons
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Scarr
authors.forename: Simone
authors.initials: S
authors.lastname: Boer
authors.forename: Tammie
authors.initials: T
authors.lastname: Money
authors.forename: Won-Je
authors.initials: WJ
authors.lastname: Jeon
authors.forename: Chris
authors.initials: C
authors.lastname: Felder
authors.forename: Brian
authors.initials: B
authors.lastname: Dean
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000378:metabolism; D010890:Pirenzepine / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000378:metabolism*; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D043588:Receptor, Muscarinic M4 / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D018727:Muscarinic Antagonists; D019275:Radiopharmaceuticals; D043643:Receptor, Muscarinic M1; D043588:Receptor, Muscarinic M4; D010890:Pirenzepine