The psychopharmacology-molecular biology interface: exploring the behavioural roles of dopamine receptor subtypes using targeted gene deletion ('knockout')

Prog Neuropsychopharmacol Biol Psychiatry. 2001 May;25(4):925-64. doi: 10.1016/s0278-5846(01)00152-x.


In the absence of selective agonists and antagonists able to discriminate between individual members of the D1-like and D2-like families of dopamine receptor subtypes, functional parcellation has remained problematic. 'Knockout' of these subtypes by targeted gene deletion offers a new approach to evaluating their roles in the regulation of behaviour. Like any new technique, 'knockout' has associated with it a number of methodological limitations that are now being addressed in a systematic manner. Studies on the phenotype of D1(A/1), D(1B/5), D2, D3 and D4 'knockouts' at the level of spontaneous and agonist/antagonist-induced behaviour are reviewed, in terms of methodological issues, neuronal implications and potential clinical relevance. Dopamine receptor subtype 'knockout' is a nascent technology that is now beginning to fulfil its potential. It is being complemented by more systematic phenotypic characterisation at the level of behaviour and additional, molecular biologically-based approaches.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Deletion*
  • Humans
  • Mice
  • Mice, Knockout
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / genetics*
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D3
  • Receptors, Dopamine D4


  • DRD3 protein, human
  • DRD4 protein, human
  • Drd3 protein, mouse
  • Drd4 protein, mouse
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Receptors, Dopamine D4