Nigrostriatal dopaminergic activities in dementia with Lewy bodies in relation to neuroleptic sensitivity: comparisons with Parkinson's disease

Biol Psychiatry. 1998 Oct 15;44(8):765-74. doi: 10.1016/s0006-3223(98)00127-9.


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.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Autoradiography
  • Brain / pathology
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology
  • Cell Count
  • Dopamine / metabolism*
  • Female
  • Homovanillic Acid / metabolism
  • Humans
  • Male
  • Neostriatum / metabolism*
  • Neostriatum / pathology
  • Neurons / metabolism
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Receptors, Dopamine D2 / metabolism
  • Substantia Nigra / metabolism*
  • Substantia Nigra / pathology


  • Antipsychotic Agents
  • Receptors, Dopamine D2
  • Dopamine
  • Homovanillic Acid