Dopamine receptor functions: lessions from knockout mice

In the past few years, a number of laboratories have used gene targeting via homologous recombination to generate mice deficient for key molecules involved in dopaminergic (DAergic) transmission. This tremendous effort has resulted in the successful generation and characterization of mice deficient for the neurotransmitter DA, the main terminator of DAergic neurotransmission (the DA transporter), and all five subtypes of DA receptors. This review summarizes the results from studies of the various DA receptor knockout mice and of mice deficient in proteins that mediate DA receptor signaling. It focuses on a comparison of the locomotor phenotypes and responses to drugs of abuse (psychostimulants), and reviews the results of anatomic studies examining the morphological and neurochemical differentiation of the striatum in these mutants. Moreover, an overview of recently published results highlighting the physiological relevance of the interaction between different DA receptors and between DA receptors and other neurotransmitter receptors in the modulation of behavioral and molecular responses to DAergic stimulation is presented. Finally, in view of the recently discovered heteroligomeric assemblies of neurotransmitter receptors that involve DA receptor subtypes, the potential value of knockout mice as a tool for testing the in vivo significance of these heteroligomeric receptors is discussed. (C) 2001 Elsevier Science Inc. All rights reserved.