NIGROSTRIATAL DOPAMINERGIC ACTIVITIES IN DEMENTIA WITH LEWY BODIES INRELATION TO NEUROLEPTIC SENSITIVITY - COMPARISONS WITH PARKINSONS-DISEASE

Background: In dementia with Lewy bodies (DLB) mild extrapyramidal sym ptoms are associated with moderate reductions in substantia nigra neur on density and concentration of striatal dopamine. Many DLB patients t reated with typical neuroleptics suffer severe adverse reactions, whic h result in decreased survival. Methods: In a series of DLB cases, wit h and without neuroleptic sensitivity, substantia nigra neuron densiti es, striatal dopamine and homovanillic acid concentrations, and autora diographic [H-3]mazindol and [H-3]raclopride binding (to the dopamine transporter and D2 receptor, respectively) were analyzed and compared to control and idiopathic Parkinson's disease cases. Results: D2 recep tors were up-regulated in neuroleptic-tolerant DLB and Parkinson's dis ease compared to DLB without neuroleptic exposure and controls. D2 rec eptors were not up-regulated in DLB cases with severe neuroleptic reac tions, Dopamine uptake sites were reduced concomitantly with substanti a nigra neuron density in Parkinson's disease compared to controls, bu t there was no significant correlation between substantia nigra neuron density and [H-3]mazindol binding in DLB groups. There was no signifi cant difference in substantia nigra neuron density, [H-3]mazindol bind ing, and dopamine or homovanillic acid concentration between neurolept ic-tolerant and -sensitive groups. Conclusions: Failure to up-regulate , D2 receptors in response to neuroleptic blockade or reduced dopamine rgic innervation may be the critical factor responsible for neurolepti c sensitivity. Biol Psychiatry 1998;44: 765-774 (C) 1998 Society of Bi ological Psychiatry.