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'''Dopamine''' is a [[neurotransmitter]] with multiple roles in the body. == Dopamine synthesis == Dopamine is synthesized in [[Neuron|neurons]] and the [[adrenal glands]]. L-[[Phenylalanine]] β L-[[Tyrosine]] β [[L-DOPA]] β Dopamine Dopamine is incapable of crossing the blood-brain barrier so it must be produced in the brain for neuronal activity, or peripherally for peripheral activity. Peripheral dopamine is produced by the adrenal glands and the [[gut]]. [[BH4]] is a cofactor in the conversion of L-Phenylalanine to L-Tyrosine and L-Tyrosine to L-DOPA. The availability of BH4 is dependent on the [[methylation cycle]]. Dopamine is a precursor to [[norepinephrine]] and [[epinephrine]]. [[Iron]] is important in the expression of dopamine receptors in the [[brain]]<ref>{{Cite web | url = https://pubmed.ncbi.nlm.nih.gov/6138953/ | title = Brain Iron and Dopamine Receptor Function | last = Mb | first = Youdim | last2 = D | first2 = Ben-Shachar | date = 1983 | website = Advances in biochemical psychopharmacology|language=en|pmid=6138953|access-date=2020-05-28 | last3 = R | first3 = Ashkenazi | last4 = S | first4 = Yehuda}}</ref> and is also a cofactor in for [[tyrosine hydroxylase]], the enzyme that catalyzes the conversion of tyrosine to L-DOPA. ==Nervous system== Dopamine plays a role in [[Executive function problems|executive function]], motor control, motivation, arousal. The largest source of dopamine in the brain is in the [[substantia nigra]] and [[ventral segmental area]], both components of the [[basal ganglia]]. == Immune system == Dopamine reduces systemic inflammation by blocking [[inflammasome]] activation.<ref>{{Cite journal | last = Yan | first = Yiqing | last2 = Jiang | first2 = Wei | last3 = Liu | first3 = Lei | last4 = Wang | first4 = Xiaqiong | last5 = Ding | first5 = Chen | last6 = Tian | first6 = Zhigang | last7 = Zhou | first7 = Rongbin | date = Jan 2015 | title = Dopamine Controls Systemic Inflammation through Inhibition of NLRP3 Inflammasome | url =http://www.cell.com/cell/abstract/S0092-8674(14)01524-4|journal=Cell|language=English|volume=160|issue=1-2 | pages = 62β73|doi=10.1016/j.cell.2014.11.047|issn=0092-8674|via=}}</ref><ref>{{Cite journal | last = Bordon | first = Yvonne | authorlink = | date = Feb 2015 | title = Dopamine blocks inflammasome activation | url =https://www.nature.com/articles/nri3817|journal=Nature Reviews Immunology|language=en|volume=15|issue=2 | pages = 69β69|doi=10.1038/nri3817|issn=1474-1741|pmc=|pmid=|access-date=|quote=|via=}}</ref> Dopamine has a role in the activity of [[lymphocytes]]. It activates native [[T cell|t cells]] but inhibits the activity of activated t cells.<ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856781/</ref> However, dopamine may also induce the release of [[IL-17|interleukin-17]] in [[rheumatoid arthritis]].<ref>http://www.nature.com/nrd/journal/v10/n4/full/nrd3422.html</ref> Inflammation may also have a role in dopamine production. A study of [[Hepatitis C]] patients found that [[interferon alpha]] treatment resulted in significantly increased levels of [[dihydrobiopterin]] (BH2) and decreased [[tetrahydrobiopterin]] (BH4) as well as reduced conversion of [[phenylalanine]] to [[tyrosine]] in the cerebrospinal fluid, which are associated with decreased dopamine in the brain.<ref>{{Cite web | url = https://pubmed.ncbi.nlm.nih.gov/23072726/ | title = Tyrosine Metabolism During Interferon-Alpha Administration: Association With Fatigue and CSF Dopamine Concentrations | last = Felger | first = JC | authorlink = | last2 = Li | first2 = L | authorlink2 = | date = Jul 2013 | website = Brain, behavior, and immunity|language=en|pmid=23072726| archive-url = | archive-date = |url-status = | access-date=2020-05-28 | last3 = Marvar | first3 = PJ | last4 = Woolwine | first4 = BJ | last5 = Harrison | first5 = DG | last6 = Raison | first6 = CL | last7 = Miller | first7 = AH}}</ref> == Fatigue == The [[dopamine imbalance hypothesis of fatigue in neurological disorders]] states that: "...fatigue arises [in neurological disease] due to a dopamine imbalance in the central nervous system"<ref name=":0">{{Cite journal | last = Dobryakova | first = Ekaterina | authorlink = | last2 = Genova | first2 = Helen M. | authorlink2 = | last3 = DeLuca | first3 = John | authorlink3 = | last4 = Wylie | first4 = Glenn R. | author-link4 = | date = 2015 | title=The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders |url =https://www.frontiersin.org/articles/10.3389/fneur.2015.00052/full|journal=Frontiers in Neurology|language=English|volume=6|issue= | pages = |doi=10.3389/fneur.2015.00052|issn=1664-2295|pmc = 4357260|pmid=25814977|access-date=|quote=|via=}}</ref> The dopamine hypothesis seeks to explain fatigue in [[multiple sclerosis]], Parkinson's disease, HIV and [[chronic fatigue syndrome]] and focuses on the role of central fatigue, which can be physical or mental.<ref name=":0" /> ==Chronic fatigue syndrome== Studies have found lower levels of the dopamine precursor [[tyrosine]]<ref>{{Cite journal | last = Georgiades | first = Evelina | authorlink = | last2 = Behan | first2 = Wilhelmina M.H. | authorlink2 = | last3 = Kilduff | first3 = Liam P. | author-link3 = | last4 = Hadjicharalambous | first4 = Marios | authorlink4 = | last5 = Mackie | first5 = Eileen E. | author-link5 = | last6 = Wilson | first6 = John | author-link6 = | last7 = Ward | first7 = Susan A. | last8 = Pitsiladis | first8 = Yannis P. | date = 2003-08-01 | title = Chronic fatigue syndrome: new evidence for a central fatigue disorder |url =https://portlandpress.com/clinsci/article/105/2/213/67612/Chronic-fatigue-syndrome-new-evidence-for-a|journal=Clinical Science|language=en|volume=105|issue=2 | pages = 213β218|doi=10.1042/CS20020354|issn=0143-5221|pmc=|pmid=|access-date=|quote=|via=}}</ref> and reduced activation in the [[basal ganglia]]<ref>http://www.fasebj.org/cgi/content/meeting_abstract/26/1_MeetingAbstracts/1035.20</ref><ref>{{Cite journal | last = Miller | first = Andrew H. | authorlink = | last2 = Jones | first2 = James F. | authorlink2 = | last3 = Drake | first3 = Daniel F. | author-link3 = | last4 = Tian | first4 = Hao | authorlink4 = | last5 = Unger | first5 = Elizabeth R. | author-link5 = Elizabeth Unger | last6 = Pagnoni | first6 = Giuseppe | author-link6 = | date = 2014-05-23 | title = Decreased Basal Ganglia Activation in Subjects with Chronic Fatigue Syndrome: Association with Symptoms of Fatigue | url =https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098156|journal=PLOS ONE|language=en|volume=9|issue=5| pages = e98156|doi=10.1371/journal.pone.0098156|issn=1932-6203|pmc = 4032274|pmid=24858857|access-date=|quote=|via=}}</ref>, the region of the brain with the highest concentration of dopaminergic neurons. == Fibromyalgia == Small, preliminary studies have found evidence of abnormal dopamine metabolism in the brains of [[fibromyalgia]] patients.<ref>{{Cite web | url = https://pubmed.ncbi.nlm.nih.gov/19398377/ | title = Changes in Gray Matter Density in Fibromyalgia: Correlation With Dopamine Metabolism | last = Wood | first = PB | authorlink = | last2 = Glabus | first2 = MF | authorlink2 = | date = Jun 2009 | website = The journal of pain : official journal of the American Pain Society|language=en|pmid=19398377| archive-url = | archive-date = |url-status = | access-date=2020-05-28 | last3 = R | first3 = Simpson | last4 = Jc | first4 = Patterson}}</ref><ref>{{Cite web | url = https://pubmed.ncbi.nlm.nih.gov/17023218/ | title = Reduced Presynaptic Dopamine Activity in Fibromyalgia Syndrome Demonstrated With Positron Emission Tomography: A Pilot Study | last = Wood | first = PB | authorlink = | last2 = Patterson | first2 = JC | authorlink2 = | date = Jan 2007 | website = The journal of pain : official journal of the American Pain Society|language=en|pmid=17023218| archive-url = | archive-date = |url-status = | access-date=2020-05-28 | last3 = Jj | first3 = Sunderland | last4 = Kh | first4 = Tainter | last5 = Mf | first5 = Glabus | last6 = Dl | first6 = Lilien}}</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/17610577</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/24449585</ref> ==Other conditions== [[Parkinson's disease]] involves the loss of dopaminergic neurons in the midbrain and subsequently reduced dopamine. [[Schizophrenia]], [[ADHD]] and [[restless leg syndrome]] are also associated with altered dopamine. Cerebralspinal iron is decreased in [[restless legs syndrome]] despite normal serum levels.<ref>{{Cite web | url = https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/restless-legs-syndrome/what-is-rls/causes.html | title = Causes of Restless Legs Syndrome (RLS) {{!}} The Johns Hopkins Center for Restless Legs Syndrome | last = Ciattei | first = Jennifer | website = hopkinsmedicine.org|language=en|access-date=2020-05-28}}</ref> In addition to its neurological effects, reduced dopamine may also have immunological effects in these diseases. Altered dopamine [[metabolism]] may play a role in a number of [[Autoimmune disease|autoimmune diseases]].<ref>{{Cite journal | last = Pacheco | first = Rodrigo | last2 = Contreras | first2 = Francisco | last3 = Zouali | first3 = Moncef| date = 2014 | title = The Dopaminergic System in Autoimmune Diseases |url =https://www.frontiersin.org/articles/10.3389/fimmu.2014.00117/full|journal=Frontiers in Immunology|language=English|volume=5|doi=10.3389/fimmu.2014.00117|issn=1664-3224}}</ref> Dopaminergic neurons are thought to play a role in [[epilepsy|epileptic seizures]] arising from the [[limbic system]].<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774988/</ref> ==Altering dopamine levels== Mice fed a [[ketogenic diet]] had increased activity of dopaminergic neurons.<ref>http://www.ncbi.nlm.nih.gov/pubmed/24769322</ref> == See also == * [[Neurotransmitter]] == Learn more == * [https://forums.phoenixrising.me/index.php?threads/interested-but-wary-about-mucuna-pruriens.42175/#post-682556 List of drugs and supplements with dopaminergic effects]. ==References== {{Reflist}} [[Category:Neurotransmitters and hormones]] [[Category:Neurotransmitters]] [[Category:Adrenal glands]]
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