Editing Substantia nigra (section)

===Amphetamine and trace amines===
{{See also|Amphetamine|Trace amine}}
Studies have shown that, in certain brain regions, amphetamine and trace amines increase the concentrations of dopamine in the [[synaptic cleft]], thereby heightening the response of the post-synaptic neuron.<ref name="Miller" /> The various mechanisms by which amphetamine and trace amines affect dopamine concentrations have been studied extensively, and are known to involve both [[dopamine transporter|DAT]] and [[vesicular monoamine transporter 2|VMAT2]].<ref name="Miller">{{cite journal | vauthors = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = Journal of Neurochemistry | 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="DrugBank 2">{{cite web | title=Amphetamine | url=http://www.drugbank.ca/drugs/DB00182#targets | work=DrugBank | publisher= University of Alberta | access-date=13 October 2013 | date=8 February 2013 }}</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 = Annals of the New York Academy of Sciences | volume = 1216 | issue = 1 | pages = 86–98 | date = January 2011 | pmid = 21272013 | pmc = 4183197 | doi = 10.1111/j.1749-6632.2010.05906.x | bibcode = 2011NYASA1216...86E }}</ref>  Amphetamine is similar in structure to dopamine and trace amines; as a consequence, it can enter the presynaptic neuron via {{abbr|DAT|dopamine transporter}} as well as by diffusing through the neural membrane directly.<ref name="Miller" /> Upon entering the presynaptic neuron, amphetamine and trace amines activate [[TAAR1]], which, through [[protein kinase]] signaling, induces dopamine efflux, [[phosphorylation|phosphorylation-dependent]] {{abbr|DAT|dopamine transporter}} [[endocytosis|internalization]], and non-competitive reuptake inhibition.<ref name="Miller" /><ref name="TAAR1 Review">{{cite journal | vauthors = Maguire JJ, Parker WA, Foord SM, Bonner TI, Neubig RR, Davenport AP | title = International Union of Pharmacology. LXXII. Recommendations for trace amine receptor nomenclature | journal = Pharmacological Reviews | volume = 61 | issue = 1 | pages = 1–8 | date = March 2009 | pmid = 19325074 | pmc = 2830119 | doi = 10.1124/pr.109.001107 }}</ref> Because of the similarity between amphetamine and trace amines, it is also a substrate for monoamine transporters; as a consequence, it (competitively) inhibits the reuptake of dopamine and other monoamines by competing with them for uptake, as well.<ref name="Miller" />

In addition, amphetamine and trace amines are substrates for the neuronal vesicular monoamine transporter, [[vesicular monoamine transporter 2]] (VMAT2).<ref name="E Weihe" /> When amphetamine is taken up by {{abbr|VMAT2|vesicular monoamine transporter 2}}, the vesicle releases (effluxes) dopamine molecules into the cytosol in exchange.<ref name="E Weihe" />