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, i ncluding dopamine. Previous findings as to whether these receptors are chan ged in Parkinson's disease and Alzheimer's disease are inconsistent and no previous investigations have focused on these receptors in dementia with Le wy bodies and schizophrenia, which are also associated with disorders of mo vement. The present autoradiographic study of striatal [H-3]nicotine binding in Alz heimer's and Parkinson's diseases, dementia with Lewy bodies and schizophre nia was conducted with particular reference to the potentially confounding variables of tobacco use and neuroleptic medication. [H-3]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 control s (n = 42). Although tobacco use in the control group was associated with i ncreased [H-3]nicotine binding (21-38%), and neuroleptic treatment in demen tia with Lewy bodies and Alzheimer's disease was associated with reduced [H -3]nicotine binding (up to 29%), differences between neurodegenerative dise ase 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 n euroleptic medication compared to controls who had not smoked (n = 10). In contrast, striatal [H-3]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 subgrou p that had smoked (24-49%, n = 8). The changes observed in [H-3]nicotine binding are likely to reflect the pre sence of these receptors on multiple sites within the striatum, which may b e differentially modulated in the different diseases. Further study is warr anted to explore which nicotinic receptor subunits and which neuronal compa rtments are involved in the changes in [H-3]nicotine binding reported, to a id development of potential nicotinic receptor therapy. (C) 2000 IBRO. Publ ished by Elsevier Science Ltd. All rights reserved.