Abstract

The dopamine transporter (DAT) has been identified as the principal brain receptor site best correlated with the rewarding and euphoric properties of cocaine. Cellular and subcellular localization data are important to help to elucidate the functional properties of this important brain molecule. In previous FYs, investigators in this Branch described the detailed distributions of the dopamine transporter mRNA in cells of the rat and human brains. In this FY, studies of the distribution of the DAT protein in rat brain were substantially advanced. Light-microscopy revealed details of the distribution of DAT distribution in rat brain that included remarkably dense fiber distributions in specific laminae of the frontal cerebral cortex. Ultrastructural studies of the transporter revealed that most of the DAT immunoreactivity was found in intracellular and plasma membrane localizations not readily associated with conventional synaptic specializations. These studies substantially add to information on the detailed cellular localizations of these important sites for cocaine reward, and underscore the possibility that extrasynaptic removal of dopamine provides a principal function of the DAT.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000160-01
Application #
5201668
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Yamashita, Motoyasu; Fukushima, Setsu; Shen, Hao-wei et al. (2006) Norepinephrine transporter blockade can normalize the prepulse inhibition deficits found in dopamine transporter knockout mice. Neuropsychopharmacology 31:2132-9
Drgon, Tomas; Lin, Zhicheng; Wang, Gene-Jack et al. (2006) Common human 5' dopamine transporter (SLC6A3) haplotypes yield varying expression levels in vivo. Cell Mol Neurobiol 26:875-89
Lin, Zhicheng; Walther, Donna; Yu, Xiao-Ying et al. (2005) SLC18A2 promoter haplotypes and identification of a novel protective factor against alcoholism. Hum Mol Genet 14:1393-404
Radzius, Aleksandras; Gallo, Joseph; Gorelick, David et al. (2004) Nicotine dependence criteria of the DIS and DSM-III-R: a factor analysis. Nicotine Tob Res 6:303-8
Liu, Qing-Rong; Zhang, Ping-Wu; Lin, Zhicheng et al. (2004) GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA. Biochem J 377:171-81
Uhl, George R (2004) Molecular genetic underpinnings of human substance abuse vulnerability: likely contributions to understanding addiction as a mnemonic process. Neuropharmacology 47 Suppl 1:140-7
Lin, Zhicheng; Zhang, Ping-Wu; Zhu, Xuguang et al. (2003) Phosphatidylinositol 3-kinase, protein kinase C, and MEK1/2 kinase regulation of dopamine transporters (DAT) require N-terminal DAT phosphoacceptor sites. J Biol Chem 278:20162-70
Uhl, George R (2003) Dopamine transporter: basic science and human variation of a key molecule for dopaminergic function, locomotion, and parkinsonism. Mov Disord 18 Suppl 7:S71-80
Uhl, George R; Lin, Zhicheng (2003) The top 20 dopamine transporter mutants: structure-function relationships and cocaine actions. Eur J Pharmacol 479:71-82
Hall, F Scott; Sora, I; Uhl, G R (2003) Sex-dependent modulation of ethanol consumption in vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) knockout mice. Neuropsychopharmacology 28:620-8

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