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

1. In the absence of selective agonists and antagonists able to discriminate between individual members of the D-1-like and D-2-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 D-1A/1, D-1B/5, D-2, D-3 and D-4 '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 fulfil its potential. It is being complemented by more systematic phenotypic characterisation at the level of behaviour and additional, molecular biologically-based approaches.