Editing Monoamine transporter (section)

==Psychostimulants==
DAT is also the target of several "DAT-blockers" including [[amphetamine]] and [[cocaine]].  These chemicals inhibit the action of DAT and, to a lesser extent, the other monoamine transporters, but their effects are mediated by separate mechanisms.

Monoamine transporters are established targets for many pharmacological agents that affect brain function, including the psychostimulants [[cocaine]] and [[amphetamine]].  Cocaine and amphetamine employ different mechanisms that both result in an increase in extracellular monoamines by decreasing reuptake.  Psychostimulants affect primarily DAT, although there is some inhibition at SERT and NET.  A large increase of synaptic dopamine results in an increased stimulation of target neurons believed to create the sensations of cocaine.<ref name= Torres/>

===Cocaine===
The stimulatory and euphoric effects of cocaine are created when cocaine inhibits the reuptake of dopamine by DAT, which results in an increase in extracellular dopamine.  Dopamine can then more readily bind neurons, which overstimulates the cells.  Cocaine is a non-selective, competitive inhibitor of monoamine transporters, sharing a similar mechanism with that of [[methylphenidate]].  Cocaine interacts with DAT, SERT, and NET, although the behavioral and reinforcing effects of cocaine depend on its inhibition of DAT and the increase in extracellular dopamine.<ref name= Torres/>

===Amphetamine===
In contrast, amphetamine enters the presynaptic neuron directly through the neuronal membrane or through monoamine transporters, competing for reuptake with neurotransmitters.  Once inside, it binds to [[trace amine-associated receptor 1|TAAR1]] or enters synaptic vesicles through [[vesicular monoamine transporter 2|VMAT2]].  When amphetamine binds to TAAR1, it reduces post-synaptic receptor firing rate and triggers [[protein kinase A]] and [[protein kinase C]] signaling, resulting in transporter phosphorylation.  Phosphorylated transporters then either operate in reverse or withdraw into the presynaptic neuron and cease transport.  When amphetamine enters the synaptic vesicles through VMAT2, monoamines are released into the cytosol.<ref name="Miller">{{cite journal | author = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = J. Neurochem. | volume = 116 | issue = 2 | pages = 164–76 |date=January 2011 | pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref><ref name="E Weihe">{{cite journal |vauthors=Eiden LE, Weihe E | title = VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse | journal = Ann. N. Y. Acad. Sci. | volume = 1216 | issue = 1| pages = 86–98 |date=January 2011 | pmid = 21272013 | doi = 10.1111/j.1749-6632.2010.05906.x | pmc=4183197| bibcode = 2011NYASA1216...86E }}</ref>