Muscarinic M2 and M4 receptors in anterior cingulate cortex: relation to neuropsychiatric symptoms in dementia with Lewy bodies.
Alterations in cholinergic functions have been reported to be associated with neuropsychiatric symptoms in dementia. Increased M1 muscarinic receptor binding in temporal cortex is associated with delusions in dementia with Lewy bodies (DLB) patients and increased M2/M4 receptor binding with psychosis in Alzheimer's disease. However, the relation between M2 and M4 muscarinic receptor and psychotic symptoms in DLB is unknown. The aim of this study was to measure M2 and M4 receptors in the anterior cingulate cortex in DLB and to correlate the neurochemical findings with neuropsychiatric symptoms. Muscarinic M2 and M4 receptor levels in the anterior cingulate cortex and adjacent cortex (Brodmann's area [BA] 32) were measured separately by using a radioligand binding protocol based on binding of [(3)H]AF-DX 384 in the presence and absence of dicyclomine, a potent M4 receptor antagonist. M2 receptor binding was significantly increased, while M4 receptor binding was unchanged in the cingulate cortex and BA32 of DLB patients compared with age-matched controls. Impaired consciousness was significantly associated with increased M4 binding and delusions were significantly associated with increased M2 binding. Increased M2 and M4 receptor binding in DLB was also associated with visual hallucinations. Upregulation of M2 and M4 muscarinic receptors in cingulate and adjacent cortex may thus contribute to the development of psychosis in DLB, with potential implications for treatments with drugs acting on these receptors.
Teaktong
Thanasak
T
Institute for Ageing and Health, MRC Building, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE46BE, UK.
Piggott
Margaret A
MA
Mckeith
Ian G
IG
Perry
Robert H
RH
Ballard
Clive G
CG
Perry
Elaine K
EK
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000503:physiopathology; D003704:Dementia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D004025:Dicyclomine / Q000494:pharmacology; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D006212:Hallucinations / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011180:Postmortem Changes; D011869:Radioligand Assay / Q000379:methods; D011877:Radionuclide Imaging; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D043588:Receptor, Muscarinic M4 / Q000378:metabolism*; D014316:Tritium / Q000493:pharmacokinetics
D018727:Muscarinic Antagonists; D043585:Receptor, Muscarinic M2; D043588:Receptor, Muscarinic M4; D014316:Tritium; C065959:AFDX 384; D010890:Pirenzepine; D004025:Dicyclomine