Dopaminergic mouse mutants: Investigating the roles of the different dopamine receptor subtypes and the dopamine transporter

Abstract

This chapter focuses on the dopamine receptor and dopamine transporter knockout mice that exist and the knowledge that is obtained using these mutant mice. Five dopamine receptors and one dopamine transporter are responsible for the binding, signaling, and reuptake of the neurotransmitter dopamine. The complexity and importance of the receptors and the transporter are well documented, although the mechanisms that regulate the dopaminergic signals are far from being completely understood. The dopaminergic system is involved in locomotion, motivated behaviors, cognition, learning and memory, endocrine regulation, the renal and cardiovascular systems as well as many other biological functions yet to be discovered. Drugs that activate or block the receptors are not specific enough to distinguish the function of each dopamine receptor subtype. Rather, the drugs available recognize various receptor subtypes with slightly different affinities, making it difficult to use the drugs in vivo and to assign the resulting phenotype to just one receptor subtype. There are knockout mice for each of the dopamine receptor subtypes as well as the dopamine transporter. These mice make it possible to study the function of each of the dopamine receptors in vivo and the phenotype of the mice in the absence of one or two of these receptors. The knockout mice have been particularly useful in beginning to understand how the five receptors act and interact with respect to drug addiction, neurodegenerative diseases, psychiatric diseases, and regulation of the endocrine system to name a few examples.