Dopamine transporters

The principal mechanism for terminating dopamine signaling is reuptake by the presynaptic neuron via the dopamine transporter (DAT). Dopamine that is not taken up is metabolized by the enzymes monoamine oxidase (MAO) and catechol-O-methyl transferase... 

The main target of action of methylphenidate, the most widespread clinically used psychostimulant, is the dopamine transporter (DAT) its inhibition increases intrasynaptic dopamine concentrations. The subcortical dopamine system (mesolimbic and nigrostriatal parts) mediates the unconditioned and conditioned responses toward reinforcement. 

Therefore, dopamine transporter inhibitors exhibit less effect in the FC. There, dopamine seems to be reuptaken by the norepinephrine transporter, which dopamine actually has a higher affinity for than norepinephrine itself. 

The amphetamine-like properties of trace amines are best described for PEA which shares close structural similarity to amphetamine and can displace monoamine neurotransmitters from synaptic vesicles and trigger their release into the synaptic cleft by acting on the dopamine transporter. However, this effect is only observed at high, supra-physiological PEA concentrations and thus might not occur under physiological conditions. 

D2 D2 dopamine receptor DAT dopamine transporter K+ potassium channel TAAR1 trace amine-associated receptor 1. 

Gelernter J, Kranzler HR, Satel SL, et al Genetic association between dopamine transporter protein alleles and cocaine-induced paranoia. Neuropsychopharmacology 11 195-200, 1994... 

Malison RT, Best SE, van Dyck CH, et al Elevated striatal dopamine transporters during acute cocaine abstinence as measured by [1231] beta-CIT SPECT. Am J... 

Giros, B and Caron, MG (1993) Molecular characterization of the dopamine transporter. Trends Pharmacol. Sci. 14 43-49. 

Following the release of dopamine, the primary mode of removal from the synapse is reuptake into the presynaptic neuron via the dopamine transporter (DAT). DAT is dependent upon the energy created by the Na+/K+ pump and is a member of the Na+/Cl -dependent plasma membrane transporter family, as are the norepinephrine and 7-aminobutyric acid (GABA) transporters. Imaging studies utilizing compounds with highly specific affinity for DAT... 

Jaber M., Jones S., Giros B., Caron M. G. (1997). The dopamine transporter a crucial component regulating dopamine transmission. Mov. Disord. 12(5), 629-33. 

Figure 1.1 The dopamine transporter terminates the action of released dopamine by transport back into the presynaptic neuron. Dopamine transport occurs with the binding of one molecule of dopamine, one chloride ion, and two sodium ions to the transporter the transporter then translocates from the outside of the neuronal membrane into the inside of the neuron.22 Cocaine appears to bind to the sodium ion binding site. This changes the conformation of the chloride ion binding site thus dopamine transport does not occur. This blockade of dopamine transport potentiates dopaminergic neurotransmission and may be the basis for the rewarding effects of cocaine.

ABUSED DRUGS AND GENETIC POLYMORPHISM OF THE DOPAMINE TRANSPORTER... 

Rostene, W., Boja, J.W., Scherman, D., Carroll, F.I., and Kuhar, M.J., Dopamine transport pharmacological distinction between the synaptic membrane and vesicular transporter in rat striatum, Eur. J. Pharmacol., 281, 175, 1992. 

Kitayama, S., Shimada, S., Xu, H., Markham, L., Donovan, D.M., and Uhl, G.R., Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding, Proc. Natl. Acad. Sci. U.S.A., 89, 7782, 1992. 

Ritz, M.C., Lamb, R.J., Goldberg, S.R., and Kuhar, M.J., Cocaine receptors on dopamine transporters are related to self-administration of cocaine, Science, 237, 1219, 1987. 

Staley, J.K., Boja, J.W., Carroll, F.I., Seltzman, H.H., Wyrick, C.D., Lewin, A.H., Abraham, P., and Mash, D.C., Mapping dopamine transporters in the human brain with novel selective cocaine analog [125I]RTI-121, Synapse, 21, 364, 1995. 

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