TY - JOUR
T1 - Nigrostriatal dopaminergic activities in dementia with lewy bodies in relation to neuroleptic sensitivity
T2 - Comparisons with Parkinson's disease
AU - Piggott, Margaret A.
AU - Perry, Elaine K.
AU - Marshall, Elizabeth F.
AU - McKeith, Ian G.
AU - Johnson, Mary
AU - Melrose, Heather L.
AU - Court, Jennifer A.
AU - Lloyd, Stephen
AU - Fairbairn, Andrew
AU - Brown, Andrew
AU - Thompson, Peter
AU - Perry, Robert H.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998/10/15
Y1 - 1998/10/15
N2 - Background: In dementia with Lewy bodies (DLB) mild extrapyramidal symptoms are associated with moderate reductions in substantia nigra neuron density and concentration of striatal dopamine. Many DLB patients treated with typical neuroleptics suffer severe adverse reactions, which result in decreased survival. Methods: In a series of DLB cases, with and without neuroleptic sensitivity, substantia nigra neuron densities, striatal dopamine and homovanillic acid concentrations, and autoradiographic [3H]mazindol and [3H]raclopride binding (to the dopamine transporter and D2 receptor, respectively) were analyzed and compared to control and idiopathic Parkinson's disease cases. Results: D2 receptors were up-regulated in neuroleptic-tolerant DLB and Parkinson's disease compared to DLB without neuroleptic exposure and controls. D2 receptors were not up-regulated in DLB cases with severe neuroleptic reactions. Dopamine uptake sites were reduced concomitantly with substantia nigra neuron density in Parkinson's disease compared to controls, but there was no significant correlation between substantia nigra neuron density and [3H]mazindol binding in DLB groups. There was no significant difference in substantia nigra neuron density, [3H]mazindol binding, and dopamine or homovanillic acid concentration between neuroleptic-tolerant and -sensitive groups. Conclusions: Failure to up-regulate D2 receptors in response to neuroleptic blockade or reduced dopaminergic innervation may be the critical factor responsible for neuroleptic sensitivity.
AB - Background: In dementia with Lewy bodies (DLB) mild extrapyramidal symptoms are associated with moderate reductions in substantia nigra neuron density and concentration of striatal dopamine. Many DLB patients treated with typical neuroleptics suffer severe adverse reactions, which result in decreased survival. Methods: In a series of DLB cases, with and without neuroleptic sensitivity, substantia nigra neuron densities, striatal dopamine and homovanillic acid concentrations, and autoradiographic [3H]mazindol and [3H]raclopride binding (to the dopamine transporter and D2 receptor, respectively) were analyzed and compared to control and idiopathic Parkinson's disease cases. Results: D2 receptors were up-regulated in neuroleptic-tolerant DLB and Parkinson's disease compared to DLB without neuroleptic exposure and controls. D2 receptors were not up-regulated in DLB cases with severe neuroleptic reactions. Dopamine uptake sites were reduced concomitantly with substantia nigra neuron density in Parkinson's disease compared to controls, but there was no significant correlation between substantia nigra neuron density and [3H]mazindol binding in DLB groups. There was no significant difference in substantia nigra neuron density, [3H]mazindol binding, and dopamine or homovanillic acid concentration between neuroleptic-tolerant and -sensitive groups. Conclusions: Failure to up-regulate D2 receptors in response to neuroleptic blockade or reduced dopaminergic innervation may be the critical factor responsible for neuroleptic sensitivity.
KW - D2 receptors
KW - Dementia with Lewy bodies
KW - Dopamine
KW - Dopamine uptake sites
KW - Neuroleptic sensitivity
KW - Parkinson's disease
KW - Substantia nigra
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U2 - 10.1016/S0006-3223(98)00127-9
DO - 10.1016/S0006-3223(98)00127-9
M3 - Article
C2 - 9798081
AN - SCOPUS:0032532714
SN - 0006-3223
VL - 44
SP - 765
EP - 774
JO - Biological psychiatry
JF - Biological psychiatry
IS - 8
ER -