Widespread decreases in cortical muscarinic receptors in a subset of people with schizophrenia

Andrew Stuart Gibbons, Elizabeth Scarr, Simone Boer, Tammie Money, Won Je Jeon, Chris Felder, Brian Dean

Research output: Contribution to journalArticleResearchpeer-review

36 Citations (Scopus)

Abstract

These studies were undertaken to investigate the selectivity of cortical muscarinic receptor radioligand binding in muscarinic M1 and M4 receptor knockout mice and to determine whether a marked decrease in [ 3H]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, [3H]pirenzepine binding was highly selective for the muscarinic M1 receptor whereas both [3H]AF-DX 386 and [ 3H]4DAMP had less discriminatory power. In addition, the data suggest that a marked decrease in [3H]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.

Original languageEnglish
Pages (from-to)37-46
Number of pages10
JournalInternational Journal of Neuropsychopharmacology
Volume16
Issue number1
DOIs
Publication statusPublished - 1 Feb 2013
Externally publishedYes

Keywords

  • Acetylcholine
  • muscarinic receptors
  • post-mortem cortex
  • schizophrenia

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