How amphetamine affects the dopamine transporter

Essential for normal central nervous system function, dopamine signaling mediates physiological functions as diverse as movement and lactation. The dopamine transporter (DAT) is involved in terminating dopamine signaling by removing the dopamine chemical messenger molecules from nerve synapses and returning them into the releasing neurons (a process called reuptake). DAT can also bind amphetamine, cocaine, and other psychostimulants, which inhibit dopamine reuptake, and, in the case of amphetamine, also stimulate the release of dopamine through DAT. It is thought that abnormal concentrations of dopamine in synapses initiate a series of events that cause the behavioral effects of these drugs. The biochemical steps underlying amphetamine-induced dopamine release, however, are not well characterized. Now, a team led by Jonathan Javitch and Aurelio Galli has identified a chemical modification of DAT that is essential for DAT-mediated dopamine release in the presence of amphetamine. Since this modification does not inhibit the ability of DAT to accumulate dopamine, it may suggest a molecular target for treating drug addiction.

Citation: Khoshbouei1 H, Sen N, Guptaroy B, Johnson L, Lund D, et al.(2004) N-Terminal Phosphorylation of the Dopamine Transporter Is Required for Amphetamine-Induced Efflux. PLoS Biol: e78 DOI: 10.1371/journal.pbio.0020078

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