The psychopharmacology-molecular biology interface: exploring the behavioural roles of dopamine receptor subtypes using targeted gene deletion ('knockout').
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.
Waddington
J L
JL
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin.
Clifford
J J
JJ
McNamara
F N
FN
Tomiyama
K
K
Koshikawa
N
N
Croke
D T
DT
D000818:Animals; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000235:genetics*; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000235:genetics; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4
C493593:DRD3 protein, human; C493599:DRD4 protein, human; C493594:Drd3 protein, mouse; C493600:Drd4 protein, mouse; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4