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

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Abstract

  • 1.

    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.

  • 2.

    ‘Knockout’ of these subtypes by targeted gene deletion offers a new approach to evaluating their roles in the regulation of behaviour.

  • 3.

    Like any new technique, ‘knockout’ has associated with it a number of methodological limitations that are now being addressed in a systematic manner.

  • 4.

    Studies on the phenotype of D1A/1, D1B/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.

  • 5.

    Dopamine receptor subtype ‘knockout’ is a nascent technology that is now beginning to fulfill its potential. It is being complemented by more systematic phenotypic characterisation at the level of behaviour and additional, molecular biologically-based approaches.

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