title: Living without DAT: Loss and compensation of the dopamine transporter gene in sauropsids (birds and reptiles).
abstract: The dopamine transporter (DAT) is a major regulator of synaptic dopamine (DA) availability. It plays key roles in motor control and motor learning, memory formation, and reward-seeking behavior, is a major target of cocaine and methamphetamines, and has been assumed to be conserved among vertebrates. We have found, however, that birds, crocodiles, and lizards lack the DAT gene. We also found that the unprecedented loss of this important gene is compensated for by the expression of the noradrenaline transporter (NAT) gene, and not the serotonin transporter genes, in dopaminergic cells, which explains the peculiar pharmacology of the DA reuptake activity previously noted in bird striatum. This unexpected pattern contrasts with that of ancestral vertebrates (e.g. fish) and mammals, where the NAT gene is selectively expressed in noradrenergic cells. DA circuits in birds/reptiles and mammals thus operate with an analogous reuptake mechanism exerted by different genes, bringing new insights into gene expression regulation in dopaminergic cells and the evolution of a key molecular player in reward and addiction pathways.
authors.affiliation: Department of Behavioral Neuroscience; Oregon Health &Science University; Portland, OR 97239-3098; USA.
authors.forename: P V
authors.initials: PV
authors.lastname: Lovell
authors.affiliation: Department of Behavioral Neuroscience; Oregon Health &Science University; Portland, OR 97239-3098; USA.|Department of Biology; Portland State University; Portland, OR 97207-0751; USA.
authors.forename: B
authors.initials: B
authors.lastname: Kasimi
authors.affiliation: Department of Behavioral Neuroscience; Oregon Health &Science University; Portland, OR 97239-3098; USA.|Present address: Biology Program; University of Utah; Salt Lake City, UT 84112-9057; USA.
authors.forename: J
authors.initials: J
authors.lastname: Carleton
authors.affiliation: Department of Behavioral Neuroscience; Oregon Health &Science University; Portland, OR 97239-3098; USA.|Present address: Institute; Federal University of Rio Grande do Norte, Natal, RN 59056-450; Brazil.
authors.forename: T A
authors.initials: TA
authors.lastname: Velho
authors.affiliation: Department of Behavioral Neuroscience; Oregon Health &Science University; Portland, OR 97239-3098; USA.
authors.forename: C V
authors.initials: CV
authors.lastname: Mello
mesh_terms: D000818:Animals; D001717:Birds; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D012104:Reptiles
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D004298:Dopamine