Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors

Nature. 1995 Oct 5;377(6548):424-8. doi: 10.1038/377424a0.


Dopaminergic neuronal pathways arise from mesencephalic nuclei and project axons to the striatum, cortex, limbic system and hypothalamus. Through these pathways dopamine affects many physiological functions, such as the control of coordinated movement and hormone secretion. Here we have studied the physiological involvement of the dopamine D2 receptors in dopaminergic transmission, using homologous recombination to generate D2-receptor-deficient mice. Absence of D2 receptors leads to animals that are akinetic and bradykinetic in behavioural tests, and which show significantly reduced spontaneous movements. This phenotype presents analogies with symptoms characteristic of Parkinson's disease. Our study shows that D2 receptors have a key role in the dopaminergic control of nervous function. These mice have therapeutic potential as a model for investigating and correcting dysfunctions of the dopaminergic system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Cell Line
  • Cloning, Molecular
  • Disease Models, Animal
  • Dopamine / metabolism
  • Female
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity
  • Neuropeptides / biosynthesis
  • Neuropeptides / genetics
  • Ovary / metabolism
  • Parkinson Disease / metabolism*
  • Parkinson Disease / physiopathology
  • RNA / metabolism
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / deficiency
  • Receptors, Dopamine D2 / physiology*
  • Testis / metabolism


  • Neuropeptides
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • RNA
  • Dopamine