Widespread decreases in cortical muscarinic receptors in a subset of people with schizophrenia
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 schizophre...
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| Veröffentlicht in: | The international journal of neuropsychopharmacology 2013-02, Vol.16 (1), p.37-46 |
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| container_title | The international journal of neuropsychopharmacology |
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| creator | Gibbons, Andrew Stuart Scarr, Elizabeth Boer, Simone Money, Tammie Jeon, Won-Je Felder, Chris Dean, Brian |
| description | 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. |
| doi_str_mv | 10.1017/S1461145712000028 |
| format | Article |
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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.</description><identifier>ISSN: 1461-1457</identifier><identifier>EISSN: 1469-5111</identifier><identifier>DOI: 10.1017/S1461145712000028</identifier><identifier>PMID: 22338582</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Adult ; Aged ; Animals ; Cerebral Cortex - metabolism ; Cerebral Cortex - pathology ; Cohort Studies ; Female ; Humans ; Male ; Mice ; Mice, Knockout ; Middle Aged ; Muscarinic Antagonists - metabolism ; Pirenzepine - metabolism ; Protein Binding - physiology ; Radioligand Assay ; Radiopharmaceuticals - metabolism ; Receptor, Muscarinic M1 - metabolism ; Receptor, Muscarinic M4 - metabolism ; Schizophrenia - metabolism ; Schizophrenia - pathology ; Young Adult</subject><ispartof>The international journal of neuropsychopharmacology, 2013-02, Vol.16 (1), p.37-46</ispartof><rights>CINP 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-bc153b459a89f7bb38701e0fb74f8e51fe8ad4a341abc0c864a7743ae94b17763</citedby><cites>FETCH-LOGICAL-c416t-bc153b459a89f7bb38701e0fb74f8e51fe8ad4a341abc0c864a7743ae94b17763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22338582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gibbons, Andrew Stuart</creatorcontrib><creatorcontrib>Scarr, Elizabeth</creatorcontrib><creatorcontrib>Boer, Simone</creatorcontrib><creatorcontrib>Money, Tammie</creatorcontrib><creatorcontrib>Jeon, Won-Je</creatorcontrib><creatorcontrib>Felder, Chris</creatorcontrib><creatorcontrib>Dean, Brian</creatorcontrib><title>Widespread decreases in cortical muscarinic receptors in a subset of people with schizophrenia</title><title>The international journal of neuropsychopharmacology</title><addtitle>Int. J. Neuropsychopharm</addtitle><description>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. 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| ispartof | The international journal of neuropsychopharmacology, 2013-02, Vol.16 (1), p.37-46 |
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| source | MEDLINE; Access via Oxford University Press (Open Access Collection); EZB-FREE-00999 freely available EZB journals |
| subjects | Adult Aged Animals Cerebral Cortex - metabolism Cerebral Cortex - pathology Cohort Studies Female Humans Male Mice Mice, Knockout Middle Aged Muscarinic Antagonists - metabolism Pirenzepine - metabolism Protein Binding - physiology Radioligand Assay Radiopharmaceuticals - metabolism Receptor, Muscarinic M1 - metabolism Receptor, Muscarinic M4 - metabolism Schizophrenia - metabolism Schizophrenia - pathology Young Adult |
| title | Widespread decreases in cortical muscarinic receptors in a subset of people with schizophrenia |
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