Nigrostriatal dopaminergic activities in dementia with Lewy bodies in relation to neuroleptic sensitivity: comparisons with Parkinson's disease.
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 neuroleptictolerant 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.
Piggott
M A
MA
Neurochemical Pathology Unit, Medical Research Council, Newcastle General Hospital, Newcastle upon Tyne, United Kingdom.
Perry
E K
EK
Marshall
E F
EF
McKeith
I G
IG
Johnson
M
M
Melrose
H L
HL
Court
J A
JA
Lloyd
S
S
Fairbairn
A
A
Brown
A
A
Thompson
P
P
Perry
R H
RH
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001345:Autoradiography; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D004298:Dopamine; D006719:Homovanillic Acid