Editing Substantia nigra (section)

===Cocaine===
{{See also|Cocaine}}
[[Cocaine]]'s mechanism of action in the human brain includes the inhibition of dopamine reuptake,<ref>{{cite journal | vauthors = Heikkila RE, Cabbat FS, Duvoisin RC | title = Motor activity and rotational behavior after analogs of cocaine: correlation with dopamine uptake blockade | journal = Communications in Psychopharmacology | volume = 3 | issue = 5 | pages = 285–90 | year = 1979 | pmid = 575770 }}</ref> which accounts for cocaine's addictive properties, as dopamine is the critical neurotransmitter for reward. However, cocaine is more active in the dopaminergic neurons of the [[ventral tegmental area]] than the substantia nigra. Cocaine administration increases metabolism in the substantia nigra, which can explain the altered motor function seen in cocaine-using subjects.<ref>{{cite book |title=Cocaine | first1 = Joan M. | last1 = Lakoski | first2 = Matthew P. | last2 = Galloway | first3 = Francis J. | last3 = White | name-list-style = vanc |publisher=Telford Press |year=1991 |isbn=978-0-8493-8813-2}}</ref> The inhibition of dopamine reuptake by cocaine also inhibits the firing of spontaneous action potentials by the pars compacta.<ref>{{cite journal | vauthors = Lacey MG, Mercuri NB, North RA | title = Actions of cocaine on rat dopaminergic neurones in vitro | journal = British Journal of Pharmacology | volume = 99 | issue = 4 | pages = 731–5 | date = April 1990 | pmid = 2361170 | pmc = 1917549 | doi = 10.1111/j.1476-5381.1990.tb12998.x }}</ref> The mechanism by which cocaine inhibits dopamine reuptake involves its binding to the [[dopamine transporter]] protein. However, studies show that cocaine can also cause a decrease in DAT [[mRNA]] levels,<ref name="coke">{{cite journal | vauthors = Xia Y, Goebel DJ, Kapatos G, Bannon MJ | title = Quantitation of rat dopamine transporter mRNA: effects of cocaine treatment and withdrawal | journal = Journal of Neurochemistry | volume = 59 | issue = 3 | pages = 1179–82 | date = September 1992 | pmid = 1494906 | doi = 10.1111/j.1471-4159.1992.tb08365.x | s2cid = 34068876 }}</ref> most likely due to cocaine blocking dopamine receptors rather than direct interference with transcriptional or translational pathways.<ref name = coke/>

Inactivation of the substantia nigra could prove to be a possible treatment for cocaine addiction. In a study of cocaine-dependent rats, inactivation of the substantia nigra via implanted [[cannulae]] greatly reduced cocaine addiction relapse.<ref>{{cite journal | vauthors = See RE, Elliott JC, Feltenstein MW | title = The role of dorsal vs ventral striatal pathways in cocaine-seeking behavior after prolonged abstinence in rats | journal = Psychopharmacology | volume = 194 | issue = 3 | pages = 321–31 | date = October 2007 | pmid = 17589830 | doi = 10.1007/s00213-007-0850-8 | s2cid = 12652533 }}</ref>