Dopamine Receptors and Behavior: From Psychopharmacology to Mutant Models

Elucidating the relative involvement of individual dopamine receptor subtypes in the regulation of behavior has been made difficult by anomalies at the psychopharmacology–molecular biology interface; specifically, the extent to which gene cloning has revealed greater diversity in dopamine receptor typology beyond the original D1/D2 classification, to include individual members of D1-like (D1 and D5) and D2-like (D2Short, D2Long, D3, and D4) families, has not been matched by similar progress in developing selective agonists and antagonists for these receptors. Thus, although classical psychopharmacological approaches have been instrumental in defining dopamine-dependent behaviors at the family level, more incisive molecular genetic techniques have been required to determine the functional roles of the individual members of these families. This chapter seeks to (a) summarize the classical psychopharmacology of dopamine receptor subtype function, (b) provide an overview of recent findings in dopamine receptor subtype knockouts across several domains of behavior, and (c) interpret new insights in the context of the limitations of these techniques and prior knowledge of the regulation of behavior by dopamine receptors.