Mutant Mice Lacking Dopamine Receptor Genes
Dopamine is the principle neurotransmitter for several neural systems in the brain. The dopaminergic system is involved in the inhibitory regulation of the secretion of several peptide hormones in the pituitary as well as in the modulation of motor activity via the nigrostriatal dopaminergic pathway. Dopaminergic system is also implicated in motivated behaviors, emotional stability, and certain aspects of learning and memory. So far, five subtypes of dopamine receptor, designated as D1R to D5R, have been found by cloning. These receptors have been divided into two major classes, referred to as D1-like (D1 and D5) and D2-like (D2, D3 and D4) receptors originally based on their pharmacological properties and on their opposite coupling of either up or down regulation to the adenylyl cyclase and cAMP production pathway (Civelli et al., 1993; Gingrich and Caron, 1993). The D1-like receptors are mainly expressed in the caudate putamen, nucleus accumbens, olfactory tubercle, cerebral cortex and hippocampus, while the D2-like receptors are mainly expressed in the caudate putamen, nucleus accumbens, olfactory tubercle, and the pituitary. The D2-like receptors are also expressed on dopaminergic cell bodies within the substantia nigra compacta, ventral tegmental areas, and on the terminals. In order to investigate the selective physiological role of each of dopamine receptor, we generated mutant mice which lack each of five dopamine receptors.