Nicotine binding in human striatum: elevation in schizophrenia and reductions in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease and in relation to neuroleptic medication.
Striatal nicotinic acetylcholine receptors with high affinity for nicotinic agonists are involved with the release of a number of neurotransmitters, including dopamine. Previous findings as to whether these receptors are changed in Parkinson's disease and Alzheimer's disease are inconsistent and no previous investigations have focused on these receptors in dementia with Lewy bodies and schizophrenia, which are also associated with disorders of movement. The present autoradiographic study of striatal [3H]nicotine binding in Alzheimer's and Parkinson's diseases, dementia with Lewy bodies and schizophrenia was conducted with particular reference to the potentially confounding variables of tobacco use and neuroleptic medication. [3H]Nicotine binding in both dorsal and ventral caudate and putamen was significantly reduced in Parkinson's disease (43-67%, n=13), Alzheimer's disease (29-37%, n=13) and dementia with Lewy bodies (50-61%, n=20) compared to age-matched controls (n=42). Although tobacco use in the control group was associated with increased [3H]nicotine binding (21-38%), and neuroleptic treatment in dementia with Lewy bodies and Alzheimer's disease was associated with reduced [3H]nicotine binding (up to 29%), differences between neurodegenerative disease groups and controls persisted in subgroups of Alzheimer's disease cases (26-33%, n=6, in the ventral striatum) and dementia with Lewy body cases (30-49%, n=7, in both dorsal and ventral striatum) who had received no neuroleptic medication compared to controls who had not smoked (n=10). In contrast, striatal [3H]nicotine binding in a group of elderly (56-85 years) chronically medicated individuals with schizophrenia (n=6) was elevated compared with the entire control group (48-78%, n=42) and with a subgroup that had smoked (24-49%, n=8). The changes observed in [3H]nicotine binding are likely to reflect the presence of these receptors on multiple sites within the striatum, which may be differentially modulated in the different diseases. Further study is warranted to explore which nicotinic receptor subunits and which neuronal compartments are involved in the changes in [3H]nicotine binding reported, to aid development of potential nicotinic receptor therapy.
Court
J A
JA
MRC Neurochemical Pathology Unit, Newcastle General Hospital, Westgate Road, NE4 6BE, Newcastle upon Tyne, UK. j.a.court@ncl.ac.uk
Piggott
M A
MA
Lloyd
S
S
Cookson
N
N
Ballard
C G
CG
McKeith
I G
IG
Perry
R H
RH
Perry
E K
EK
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism; D020961:Lewy Body Disease / Q000188:drug therapy / Q000378:metabolism; D017072:Neostriatum / Q000737:chemistry / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000032:analysis / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D012737:Sex Factors; D013569:Synapses / Q000737:chemistry / Q000378:metabolism; D014316:Tritium
D014150:Antipsychotic Agents; D009538:Nicotine; D017448:Receptors, Dopamine D2; D011978:Receptors, Nicotinic; D014316:Tritium