Dopamine 48548 225559200 2008-07-14T08:52:59Z 121.44.217.72 /* Movement */ {{otheruses}} {{Chembox new |ImageFile=Dopamin - Dopamine.svg |ImageSize= |ImageFile2=Dopamine-3d-CPK.png |ImageSize2=150px |IUPACName=4-(2-aminoethyl)benzene-1,2-diol |OtherNames=2-(3,4-dihydroxyphenyl)ethylamine;<br/> 3,4-dihydroxyphenethylamine;<br/> 3-hydroxytyramine; DA; Intropin<br/> Revivan; Oxytyramine |Section1= {{Chembox Identifiers | CASNo=51-61-6 | PubChem=681 | SMILES=C1=CC(=C(C=C1CCN)O)O }} |Section2= {{Chembox Properties | Formula=C<sub>8</sub>H<sub>11</sub>NO<sub>2</sub> | MolarMass=153.178 | Appearance= | Density= | MeltingPt=128 °C (401 K) | BoilingPt= | Solubility=60.0 g/100 ml (? °C), solid }} |Section3= {{Chembox Hazards | MainHazards= | FlashPt= | Autoignition= | RSPhrases = [[List of R-phrases|R]]: 36/37/38 <br> [[List of S-phrases|S]]: 26-36 }} }} '''Dopamine''' is a [[hormone]] and [[neurotransmitter]] occurring in a wide variety of animals, including both vertebrates and invertebrates. In the [[human brain|brain]], this [[phenethylamine]] functions as a [[neurotransmitter]], activating the five types of [[dopamine receptor]]s — D1, D2, D3, D4 and D5, and their variants. Dopamine is produced in several areas of the brain, including the [[substantia nigra]] and the [[ventral tegmental area]].<ref>http://www.encyclopedia.com/doc/1O87-ventraltegmentalarea.html Reference for VTA.</ref> Dopamine is also a [[neurohormone]] released by the [[hypothalamus]]. Its main function as a hormone is to inhibit the release of [[prolactin]] from the anterior lobe of the [[pituitary]]. Dopamine can be supplied as a [[medication]] that acts on the [[sympathetic nervous system|sympathetic]] [[nervous system]], producing effects such as increased [[heart]] rate and [[blood pressure]]. However, because dopamine cannot cross the [[blood-brain barrier]], dopamine given as a drug does not directly affect the [[central nervous system]]. To increase the amount of dopamine in the brains of patients with diseases such as [[Parkinson's disease]] and dopa-responsive [[dystonia]], L-DOPA ([[levodopa]]), which is the precursor of dopamine, can be given because it can cross the [[blood-brain barrier]]. == History == Dopamine was discovered in 1952 by [[Arvid Carlsson]] and Nils-Åke Hillarp at the Laboratory for Chemical Pharmacology of the National Heart Institute of Sweden. It was named dopamine because it was a [[monoamine]], and its synthetic precursor was 3,4-dihydroxyphenylalanine ([[L-DOPA]]).<ref> Benes, F.M. Carlsson and the discovery of dopamine.'' Trends in Pharmacological Sciences'', Volume 22, Issue 1, 1 January 2001, Pages 46-47.</ref> [[Arvid Carlsson]] was awarded the [[2000]] [[Nobel Prize in Physiology or Medicine]] for showing that dopamine is not just a precursor of [[norepinephrine]] (noradrenaline) and [[epinephrine]] (adrenaline) but a neurotransmitter, as well. Dopamine was first synthesized artificially in 1910 by George Barger and James Ewens at Wellcome Laboratories in London, England.<ref>[http://movementdisorders.org/education/onlinecme/levodopa/print.pdf Fahn, Stanley, "The History of Levodopa as it Pertains to Parkinson’s Disease," Movement Disorder Society’s 10th International Congress of Parkinson's Disease and Movement Disorders on November 1, 2006, in Kyoto, Japan.]</ref> == Biochemistry == [[Image:Catecholamines biosynthesis.svg|thumb|right|400px|Biosynthesis of Dopamine]] === Name and family === Dopamine has the chemical formula C<sub>6</sub>H<sub>3</sub>(OH)<sub>2</sub>-CH<sub>2</sub>-CH<sub>2</sub>-NH<sub>2</sub>. Its chemical name is "4-(2-aminoethyl)benzene-1,2-diol" and its abbreviation is "DA." As a member of the [[catecholamine]] family, dopamine is a precursor to [[norepinephrine]] (noradrenaline) and then [[epinephrine]] (adrenaline) in the biosynthetic pathways for these neurotransmitters. === Biosynthesis === Dopamine is biosynthesized in the body (mainly by nervous tissue and the [[adrenal medulla|medulla]] of the [[adrenal gland]]s) first by the hydroxylation of the amino acid [[L-tyrosine]] to L-DOPA via the enzyme tyrosine 3-monooxygenase, also known as [[tyrosine hydroxylase]], and then by the [[decarboxylation]] of [[L-DOPA]] by [[aromatic L-amino acid decarboxylase]] (which is often referred to as dopa decarboxylase). In some neurons, dopamine is further processed into [[norepinephrine]] by [[dopamine beta-hydroxylase]]. In [[neuron]]s, dopamine is packaged after synthesis into [[Vesicle (biology)|vesicles]], which are then released into the [[synapse]] in response to a presynaptic [[action potential]]. === Inactivation and degradation === [[Image:Dopamine degradation.svg|thumb|right|500px]] Dopamine is inactivated by reuptake via the [[dopamine transporter]], then enzymatic breakdown by [[catechol-O-methyl transferase]] (COMT) and [[monoamine oxidase]] (MAO). Dopamine that is not broken down by enzymes is repackaged into vesicles for reuse. Dopamine may also simply [[diffuse]] away from the [[synapse]], and help to regulate blood pressure. ==Functions in the brain== <!-- Neurotransmitter systems has a link to here --> Dopamine has many functions in the brain, including important roles in behavior and [[cognition]], [[motor activity]], [[motivation]] and [[reward system|reward]], inhibition of [[prolactin]] production (involved in [[lactation]]), [[sleep]], [[Mood (psychology)|mood]], [[attention]], and [[learning]]. Dopaminergic neurons (i.e., neurons whose primary neurotransmitter is dopamine) are present chiefly in the [[ventral tegmental area]] (VTA) of the [[midbrain]], [[substantia nigra|substantia nigra pars compacta]], and [[arcuate nucleus]] of the hypothalamus. The phasic responses of dopamine neurons are observed when an unexpected reward is presented. These responses transfer to the onset of a [[Classical conditioning|conditioned stimulus]] after repeated pairings with the reward. Further, dopamine neurons are depressed when the expected reward is omitted. Thus, dopamine neurons seem to [[encoding|encode]] the prediction error of rewarding outcomes. In nature, we learn to repeat behaviors that lead to maximize rewards. Dopamine is therefore believed to provide a teaching signal to parts of the brain responsible for acquiring new behavior. [[Temporal difference learning]] provides a computational model describing how the prediction error of dopamine neurons is used as a teaching signal. In insects, a similar reward system exists, using [[octopamine]], a [[Quantitative structure-activity relationship|chemical relative]] of dopamine.<ref name="octopamine-honeybee">{{cite journal |author=Barron AB, Maleszka R, Vander Meer RK, Robinson GE |title=Octopamine modulates honey bee dance behavior |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue=5 |pages=1703–7 |year=2007 |pmid=17237217 |doi=10.1073/pnas.0610506104}}</ref> === Anatomy === {{main|dopamine pathways}} [[Dopaminergic]] neurons form a [[neurotransmitter system]] which originates in [[substantia nigra pars compacta]], [[ventral tegmental area]] (VTA), and [[hypothalamus]]. These project [[axon]]s to large areas of the brain through four major pathways: * [[Mesocortical pathway]] * [[Mesolimbic pathway]] * [[Nigrostriatal pathway]] * [[Tuberoinfundibular pathway]] This innervation explains many of the effects of activating this dopamine system. For instance, the [[mesolimbic pathway]] connects the VTA and [[nucleus accumbens]], both are central to the brain [[reward system]].<ref>[http://www.pdn.cam.ac.uk/staff/schultz/ Schultz, Cambridge university, UK]</ref> === Movement === Via the [[dopamine receptor]]s D1, D2, D3, D4 and D5, dopamine reduces the influence of the indirect pathway, and increases the actions of the direct pathway within the [[basal ganglia]]. Insufficient dopamine [[biosynthesis]] in the dopaminergic neurons can cause [[Parkinson's disease]], in which a person loses the ability to execute smooth, controlled movements. === Cognition and frontal cortex === In the [[frontal lobe]]s, dopamine controls the flow of information from other areas of the brain. Dopamine disorders in this region of the brain can cause a decline in [[neurocognitive]] functions, especially [[memory]], [[attention]], and [[problem-solving]]. Reduced dopamine concentrations in the prefrontal cortex are thought to contribute to [[attention deficit disorder]]. It has been found that D1 receptors are responsible for the cognitive-enhancing effects of dopamine.<ref name="Inhibitorydopamine">{{cite journal |author=Heijtz RD, Kolb B, Forssberg H |title=Motor inhibitory role of dopamine D1 receptors: implications for ADHD. |url=http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T0P-4NTB97R-Y-1&_cdi=4868&_user=308069&_orig=search&_coverDate=09%2F30%2F2007&_sk=999079998&view=c&wchp=dGLbVzz-zSkzV&md5=c49d721e7e713190c2ac6fab7a491093&ie=/sdarticle.pdf |journal=Physiol Behav |volume=92 |issue=1-2 |pages=155–160 |year=2007 |pmid=17585966 |doi=10.1016/j.physbeh.2007.05.024 }}</ref> On the converse, however, [[anti-psychotic]] [[medication]]s act as dopamine antagonists and are used in the treatment of positive symptoms in [[schizophrenia]]. === Regulating prolactin secretion === Dopamine is the primary [[neuroendocrine]] inhibitor of the secretion of [[prolactin]] from the [[anterior pituitary]] gland. <ref name="prolactininhibition">{{cite journal |author=Ben-Jonathan N, Hnasko R |title=Dopamine as a Prolactin (PRL) Inhibitor|journal=Endocrine Reviews |volume=22 |issue=6 |pages=724–763 |year=2001| doi = 10.1210/er.22.6.724 <!--Retrieved from CrossRef by DOI bot-->|url=http://edrv.endojournals.org/cgi/reprint/22/6/724.pdf}}</ref> Dopamine produced by neurons in the [[arcuate nucleus]] of the hypothalamus is secreted into the hypothalamo-hypophysial blood vessels of the [[median eminence]], which supply the [[pituitary gland]]. The lactotrope cells that produce [[prolactin]], in the absence of dopamine, secrete prolactin continuously; dopamine inhibits this secretion. Thus, in the context of regulating prolactin secretion, dopamine is occasionally called '''prolactin-inhibiting factor''' ('''PIF'''), '''prolactin-inhibiting hormone''' ('''PIH'''), or '''prolactostatin'''. Prolactin also seems to inhibit dopamine release, such as after [[orgasm]], and is chiefly responsible for the [[Refractory period (sex)|refractory period]]. === Motivation and pleasure === {{main|motivation}} ==== Reinforcement ==== Dopamine is commonly associated with the ''pleasure system'' of the brain, providing feelings of enjoyment and [[reinforcement]] to motivate a person proactively to perform certain activities. Dopamine is released (particularly in areas such as the [[nucleus accumbens]] and [[ventral tegmental area]]) by naturally rewarding experiences such as [[food]], [[Human sexual behaviour|sex]],<ref name="PMID11805404">{{cite journal|last=Giuliano|first=F.|coauthors=Allard J.|year=2001|title=Dopamine and male sexual function|url=|journal=Eur Urol|volume=40|issue=|pages=601–608|pmid=11805404|doi=10.1159/000049844}}</ref><ref name="PMID11477488">{{cite journal|last=Giuliano|first=F.|coauthors=Allard J. |year=2001|title=Dopamine and sexual function|url=http://www.nature.com/ijir/journal/v13/n3s/index.html|journal=Int J Impot Res|volume=13|issue=Suppl 3|pages=S18–S28|doi=10.1038/sj.ijir.3900719|pmid=11477488}}</ref> drugs, and [[neutral stimulus|neutral stimuli]] that become [[Classical conditioning|associated]] with them. This theory is often discussed in terms of drugs such as [[cocaine]], [[nicotine]], and [[amphetamine]]s, which seem to directly or indirectly lead to an increase of dopamine in these areas, and in relation to [[neurobiology|neurobiological]] theories of chemical [[addiction]], arguing that these dopamine pathways are pathologically altered in addicted persons. Recent studies indicate that [[aggression]] may also stimulate the release of dopamine in this way. ==== Reuptake inhibition, expulsion ==== Cocaine and amphetamines inhibit the [[re-uptake]] of dopamine; however, they both influence separate mechanisms of action. Cocaine is a [[dopamine transporter]] blocker that competitively inhibits dopamine uptake to increase the lifetime of dopamine and augments an overabundance of dopamine (an increase of up to 150 percent) within the parameters of the dopamine neurotransmitters. Like cocaine, amphetamines increase the concentration of dopamine in the [[synapse|synaptic]] gap, but by a different mechanism. Amphetamines are similar in structure to dopamine, and so can enter the terminal button of the presynaptic neuron via its dopamine transporters as well as by diffusing through the [[neural membrane]] directly. By entering the presynaptic neuron, amphetamines force dopamine molecules out of their storage [[vesicle]]s and expel them into the synaptic gap by making the dopamine transporters work in reverse. ==== Incentive salience ==== {{main|Incentive salience}} Dopamine's role in experiencing pleasure has been questioned by several researchers. It has been argued that dopamine is more associated with anticipatory desire and motivation (commonly referred to as "wanting") as opposed to actual consummatory pleasure (commonly referred to as "liking"). Dopamine is not released when unpleasant or aversive stimuli are encountered, in effect enhancing the pleasure of avoidance or removal of the unpleasant stimuli. ==== Dopamine, learning, and reward-seeking behavior ==== Dopaminergic neurons of the midbrain are the main source of dopamine in the brain.<!----><ref name="fn5">{{cite journal | author = Arias-Carrión O, Pöppel E | title = Dopamine, learning and reward-seeking behavior | journal = Act Neurobiol Exp | volume = 67 | issue = 4 | pages = 481–488 | year = 2007|url=http://www.ane.pl/pdfdownload.php?art=6738 }}</ref> Dopamine has been shown to be involved in the control of movements, the signaling of error in prediction of reward, motivation, and cognition. Cerebral dopamine depletion is the hallmark of Parkinson's disease.<!----><ref name="fn5">{{cite journal | author = Arias-Carrión O, Freundlieb N, Oertel WH, Höglinger GU | title = Adult neurogenesis and Parkinson's disease | journal = CNS Neurol Disord Drug Targets. | volume = 6 | issue = 5 | pages = 326–335. | year = 2007 | pmid = 18045161 | doi = 10.2174/187152707783220875 <!--Retrieved from CrossRef by DOI bot-->}}</ref> Other pathological states have also been associated with dopamine dysfunction, such as schizophrenia, autism, and attention deficit hyperactivity disorder in children, as well as drug abuse. Dopamine is closely associated with reward-seeking behaviors, such as approach, consumption, and addiction.<!----><ref name="fn5">{{cite journal | author = Arias-Carrión O, Pöppel E | title = Dopamine, learning and reward-seeking behavior | journal = Act Neurobiol Exp | volume = 67 | issue = 4 | pages = 481–488 | year = 2007 | pmid = }}</ref> Recent researches suggest that the firing of dopaminergic neurons is a motivational substance as a consequence of reward-anticipation. This hypothesis is based on the evidence that, when a reward is greater than expected, the firing of certain dopaminergic neurons increases, which consequently increases desire or motivation towards the reward.<!----><ref name="fn5">{{cite journal | author = Arias-Carrión O, Pöppel E | title = Dopamine, learning and reward-seeking behavior | journal = Act Neurobiol Exp | volume = 67 | issue = 4 | pages = 481–488 | year = 2007 | pmid = }}</ref> ==== Animal studies ==== Clues to dopamine's role in motivation, desire, and pleasure have come from studies performed on animals. In one such study, rats were depleted of dopamine by up to 99 percent in the [[nucleus accumbens]] and [[neostriatum]] using 6-hydroxydopamine.<!-- --><ref name="fn5">{{cite journal | author = Berridge K, Robinson T | title = What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? | journal = Brain Res Brain Res Rev | volume = 28 | issue = 3 | pages = 309–69 | year = 1998 | pmid = 9858756 | doi = 10.1016/S0165-0173(98)00019-8 <!--Retrieved from CrossRef by DOI bot-->}}</ref> With this large reduction in dopamine, the rats would no longer eat by their own volition. The researchers then force-fed the rats food and noted whether they had the proper facial expressions indicating whether they liked or disliked it. The researchers of this study concluded that the reduction in dopamine did not reduce the rat's consummatory pleasure, only the desire to actually eat. In another study, mutant hyperdopaminergic (increased dopamine) mice show higher "wanting" but not "liking" of sweet rewards.<!-- --><ref name="fn1">{{cite journal | author = Peciña S, Cagniard B, Berridge K, Aldridge J, Zhuang X | title = Hyperdopaminergic mutant mice have higher "wanting" but not "liking" for sweet rewards. | journal = J Neurosci | volume = 23 | issue = 28 | pages = 9395–402 | year = 2003 | pmid = 14561867}}</ref> ==== The effects of drugs that reduce dopamine levels in humans ==== In humans, however, drugs that reduce dopamine activity ([[neuroleptic]]s, e.g. some [[antipsychotic]]s) have been shown to reduce motivation, and to cause [[anhedonia]] a.k.a. the inability to experience pleasure.<!-- --><ref name="fn2">{{cite journal | author = Lambert M, Schimmelmann B, Karow A, Naber D | title = Subjective well-being and initial dysphoric reaction under antipsychotic drugs - concepts, measurement and clinical relevance. | journal = Pharmacopsychiatry | volume = 36 | issue = Suppl 3| pages = S181–90 | year = 2003 | pmid = 14677077 | doi = 10.1055/s-2003-45128}}</ref> Selective D2/D3 agonists [[pramipexole]] and [[ropinirole]], used to treat [[Restless legs syndrome]], have limited anti-anhedonic properties as measured by the Snaith-Hamilton Pleasure Scale.<!-- --><ref name="fn3">{{cite journal | author = Lemke M, Brecht H, Koester J, Kraus P, Reichmann H | title = Anhedonia, depression, and motor functioning in Parkinson's disease during treatment with pramipexole. | journal = J Neuropsychiatry Clin Neurosci | volume = 17 | issue = 2 | pages = 214–20 | year = 2005 | pmid = 15939976 | url=http://neuro.psychiatryonline.org/cgi/content/full/17/2/214 | doi = 10.1176/appi.neuropsych.17.2.214}}</ref> (The Snaith-Hamilton-Pleasure-Scale (SHAPS), introduced in English in 1995, assesses self-reported [[anhedonia]] in psychiatric patients.) Additionally, users of [[stimulant]]s often have depleted dopamine levels after [[withdrawal symptoms|withdrawal]] from these addictive substances. ==== Opioid and cannabinoid transmission ==== [[Opioid]] and [[cannabinoid]] transmission instead of dopamine may modulate consummatory pleasure and food palatability (liking).<!-- --><ref name="fn4">{{cite journal | author = Peciña S, Berridge K | title = Hedonic hot spot in nucleus accumbens shell: where do mu-opioids cause increased hedonic impact of sweetness? | journal = J Neurosci | volume = 25 | issue = 50 | pages = 11777–86 | year = 2005 | pmid = 16354936 | url=http://www.jneurosci.org/cgi/content/full/jneuro;25/50/11777 | doi = 10.1523/JNEUROSCI.2329-05.2005 <!--Retrieved from CrossRef by DOI bot-->}}</ref> This could explain why animals' "liking" of food is independent of brain dopamine concentration. Other consummatory pleasures, however, may be more associated with dopamine. One study found that both anticipatory and consummatory measures of sexual behavior (male rats) were disrupted by DA receptor antagonists.<!-- --><ref name="fn6">{{cite journal | author = Pfaus J, Phillips A | title = Role of dopamine in anticipatory and consummatory aspects of sexual behavior in the male rat. | journal = Behav Neurosci | volume = 105 | issue = 5 | pages = 727–43 | year = 1991 | pmid = 1840012 | doi = 10.1037/0735-7044.105.5.727 <!--Retrieved from CrossRef by DOI bot-->}}</ref> Libido can be increased by drugs that affect dopamine, but not by drugs that affect opioid peptides or other neurotransmitters. ==== Sociability ==== Sociability is also closely tied to dopamine neurotransmission. Low D2 receptor-binding is found in people with [[social anxiety]]. Traits common to negative schizophrenia ([[social withdrawal]], [[apathy]], [[anhedonia]]) are thought to be related to a hypodopaminergic state in certain areas of the brain. In instances of [[bipolar disorder]], [[manic]] subjects can become hypersocial, as well as [[hypersexual]]. This is also credited to an increase in dopamine, because mania can be reduced by dopamine-blocking anti-psychotics. ==== Processing of pain ==== Dopamine has been demonstrated to play a role in [[pain]] processing in multiple levels of the [[central nervous system]] including the [[spinal cord]] <ref> Jensen TS, Yaksh TL.Effects of an intrathecal dopamine agonist, apomorphine, on thermal and chemical evoked noxious responses in rats.Brain Res. 1984 Apr 2;296(2):285-93 </ref>, [[periaqueductal gray]] (PAG)<ref> Flores JA, El Banoua F, Galán-Rodríguez B, Fernandez-Espejo E.Opiate anti-nociception is attenuated following lesion of large dopamine neurons of the periaqueductal grey: critical role for D1 (not D2) dopamine receptors.Pain. 2004 Jul;110(1-2):205-14. </ref>, [[thalamus]] <ref> Shyu BC, Kiritsy-Roy JA, Morrow TJ, Casey KL.Neurophysiological, pharmacological and behavioral evidence for medial thalamic mediation of cocaine-induced dopaminergic analgesia.Brain Res. 1992 Feb 14;572(1-2):216-23. </ref>, [[basal ganglia]]<ref> Chudler EH, Dong WK.The role of the basal ganglia in nociception and pain.Pain. 1995 Jan;60(1):3-38</ref> <ref> Altier N, Stewart J.The role of dopamine in the nucleus accumbens in analgesia.Life Sci. 1999;65(22):2269-87 </ref> [[insular cortex]] <ref> Burkey AR, Carstens E, Jasmin L.Dopamine reuptake inhibition in the rostral agranular insular cortex produces antinociception.J Neurosci. 1999 May 15;19(10):4169-79. </ref><ref> Coffeen U, López-Avila A, Ortega-Legaspi JM, del Angel R, López-Muñoz FJ, Pellicer F.Dopamine receptors in the anterior insular cortex modulate long-term nociception in the rat.Eur J Pain. 2008 Jul;12(5):535-43.</ref> and [[cingulate cortex]].<ref> López-Avila A, Coffeen U, Ortega-Legaspi JM, del Angel R, Pellicer F.Dopamine and NMDA systems modulate long-term nociception in the rat anterior cingulate cortex.Pain. 2004 Sep;111(1-2):136-43. </ref> Accordingly, decreased levels of dopamine have been associated with painful symptoms that frequently occur in [[Parkinson's disease]].<ref> Brefel-Courbon C, Payoux P, Thalamas C, Ory F, Quelven I, Chollet F, Montastruc JL, Rascol O.Effect of levodopa on pain threshold in Parkinson's disease: a clinical and positron emission tomography study.Mov Disord. 2005 Dec;20(12):1557-63. </ref> Abnormalities in dopaminergic neurotransmission have also been demonstrated in painful clinical conditions, including [[burning mouth syndrome]],<ref> Jääskeläinen SK, Rinne JO, Forssell H, Tenovuo O, Kaasinen V, Sonninen P, Bergman J.Role of the dopaminergic system in chronic pain -- a fluorodopa-PET study.Pain. 2001 Feb 15;90(3):257-60. </ref> [[fibromyalgia]] <ref> Wood PB, Patterson JC 2nd, Sunderland JJ, Tainter KH, Glabus MF, Lilien DL.Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study.J Pain. 2007 Jan;8(1):51-8.</ref> <ref> Wood PB, Schweinhardt P, Jaeger E, Dagher A, Hakyemez H, Rabiner EA, Bushnell MC, Chizh BA.Fibromyalgia patients show an abnormal dopamine response to pain.Eur J Neurosci. 2007 Jun;25(12):3576-82. </ref> and [[restless legs syndrome]].<ref> Cervenka S, Pålhagen SE, Comley RA, Panagiotidis G, Cselényi Z, Matthews JC, Lai RY, Halldin C, Farde L.Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding.Brain. 2006 Aug;129(Pt 8):2017-28. </ref> In general, the analgesic capacity of dopamine occurs as a result of dopamine D2 receptor activation; however, exceptions to this exist in the PAG, in which dopamine D1 receptor activation attenuates pain presumabley ''via'' activation of neurons involved in descending inhibition.<ref>Wood PB.Role of central dopamine in pain and analgesia.Expert Rev Neurother. 2008 May;8(5):781-97.</ref> In addition, D1 receptor activation in the insular cortex appears to attenuate subsequent pain-related behavior. ==== Salience ==== Dopamine may also have a role in the [[Salience (neuroscience)|salience]] ('noticeableness') of perceived objects and events, with potentially important stimuli such as: 1) rewarding things or 2) dangerous or threatening things seeming more noticeable or important.<ref>{{cite journal | author = Schultz W | title = Getting formal with dopamine and reward | journal = Neuron | volume = 36 | issue = 2 | pages = 241–263 | year = 2002 | pmid = 12383780 | doi = 10.1016/S0896-6273(02)00967-4 <!--Retrieved from CrossRef by DOI bot-->}}</ref> This hypothesis argues that dopamine assists decision-making by influencing the priority, or level of desire, of such stimuli to the person concerned. ==== Behavior disorders ==== [[Pharmacology|Pharmacological]] blockade of brain dopamine receptors increases rather than decreases drug-taking behavior. Since blocking dopamine decreases desire, the increase in drug-taking behaviour may be seen as not a chemical desire but as a deeply psychological desire to just 'feel something'. Deficits in dopamine levels are implicated in [[attention-deficit hyperactivity disorder]] (ADHD), and stimulant medications used to successfully treat the disorder increase dopamine neurotransmitter levels, leading to decreased symptoms. === Latent inhibition and creative drive === Dopamine in the [[mesolimbic pathway]] increases general [[arousal]] and goal directed behaviors and decreases [[latent inhibition]]; all three effects increase the creative drive of idea generation. This has led to a three-factor model of [[creativity]] involving the [[frontal lobe]]s, the [[temporal lobe]]s, and mesolimbic dopamine.<ref>{{cite journal | author= Flaherty, A.W, | year = 2005 | journal = Journal of Comparative Neurology | title = Frontotemporal and dopaminergic control of idea generation and creative drive | volume = 493 | issue = 1 | pages = 147–153 | pmid = 16254989 | doi = 10.1002/cne.20768 <!--Retrieved from CrossRef by DOI bot-->}}</ref> == Links to psychosis == {{main|Dopamine hypothesis of psychosis}} Abnormally high dopamine action has also been strongly linked to [[psychosis]] and [[schizophrenia]]<!-- -->,<ref>{{cite web |publisher=St. Jude Children's Research Hospital |title=Disruption of gene interaction linked to schizophrenia | accessdate=2006-07-06 | url=http://www.innovations-report.com/html/reports/life_sciences/report-52499.html}}</ref> Dopamine neurons in the [[mesolimbic pathway]] are particularly associated with these conditions. Evidence comes partly from the discovery of a class of drugs called the [[phenothiazine]]s (which block D<sub>2</sub> [[dopamine receptor]]s) that can reduce psychotic symptoms, and partly from the finding that drugs such as [[amphetamine]] and [[cocaine]] (which are known to greatly increase dopamine levels) can cause psychosis.<ref>{{cite journal | last = Lieberman | first = J.A. | coauthors = JM Kane, J. Alvir | title = Provocative tests with psychostimulant drugs in schizophrenia. | journal = Psychopharmacology (Berl). | volume = 91 | issue = 4 | pages = 415–433 | publisher = | date = 1997 | url = http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=2884687&query_hl=1&itool=pubmed_DocSum | doi = | pmid = 2884687 | accessdate = 2007-10-16 }}</ref> Because of this, most modern [[antipsychotic]] medications, for example, [[Risperidone]], are designed to block dopamine function to varying degrees. == Therapeutic use == {{main|L-DOPA}} [[L-DOPA|Levodopa]] is a dopamine precursor used in various forms to treat [[Parkinson's disease]] and dopa-responsive [[dystonia]]. It is typically co-administered with an inhibitor of peripheral decarboxylation (DDC, [[Aromatic-L-amino-acid decarboxylase|dopa decarboxylase]]), such as [[carbidopa]] or [[benserazide]]. Inhibitors of alternative metabolic route for dopamine by [[catechol-O-methyl transferase]] are also used. These include [[entacapone]] and [[tolcapone]]. The effects of dopamine, also known as [[Intropin]], are dose dependent. Dosages from 2 mcg/kg/min to 5 mcg/kg/min are considered the "renal dose." It is thought that, at this low dosage level, dopamine binds dopaminergic receptors in the kidney, dilating renal blood vessels and increasing renal blood flow. Dopamine therefore has a diuretic effect, potentially increasing urine output from 5 ml/kg/hr to 10 ml/kg/hr. Dopamine is also a positive [[inotrope|inotropic]] (and [[chronotrope|chronotropic]]) drug, and thus is used in patients with [[Shock (medical)|shock]] to increase [[cardiac output]] and [[blood pressure]]. Dopamine begins to affect the heart at the lower doses, from about 3 mcg/kg/min IV. Dopamine given at 10 mcg/kg/min to 20 mcg/kg/min is the "pressor" dose. This dose causes the greatest level of vasoconstriction, increases blood pressure and heart rate the most, but can cause the vessels in the kidneys to constrict to the point where they will become non-functional. This dose also greatly increases [[systemic vascular resistance]], and can greatly decrease peripheral perfusion. == Dopamine and fruit browning == [[Polyphenol oxidase]]s (PPOs) are a family of enzymes responsible for the [[Browning (chemical process)|browning]] of fresh fruits and vegetables when they are cut or bruised. These enzymes use molecular [[oxygen]] (O<sub>2</sub>) to [[redox|oxidise]] various [[diphenol|1,2-diphenols]] to their corresponding [[quinone]]s. The natural substrate for PPOs in [[banana]]s is dopamine. The product of their oxidation, dopamine quinone, spontaneously oxidises to other quinones. The quinones then [[polymerisation|polymerise]] and [[condense]] with [[amino acid]]s and [[protein]]s to form brown [[biological pigment|pigments]] known as [[melanin]]s. The quinones and melanins derived from dopamine may help protect damaged fruit and vegetables against growth of [[bacteria]] and [[fungi]].<ref name="mayer">{{cite journal | author = Mayer, AM | title = Polyphenol oxidases in plants and fungi: Going places? A review | journal = Phytochemistry | year=2006 | volume=67 | pages=2318–2331 | pmid = 16973188 | doi = 10.1016/j.phytochem.2006.08.006 <!--Retrieved from CrossRef by DOI bot-->}}</ref> == References == {{Reflist|2}} == See also == <div style="-moz-column-count:3; column-count: 3;"> * [[Addiction]] * [[Amphetamine]] * [[Antipsychotic]] * [[Catecholamine]] * [[Catechol-O-methyl transferase]] * [[Classical conditioning]] * [[Operant conditioning]] * [[Cocaine]] * [[Depression (mood)|Depression]] * [[Dopamine hypothesis of schizophrenia]] * [[Dopamine reuptake inhibitor]]s * [[Methylphenidate]] * [[Neurotransmitter]] * [[Parkinson's disease]] * [[Prolactinoma]] * [[Schizophrenia]] * [[Selegiline]] * [[Serotonin]]</div> == External links == * {{DrugBank|APRD00085}} {{Wiktionarypar|Dopamine}} {{Phenethylamines}} {{Cardiac stimulants excluding cardiac glycosides}} [[Category:Catecholamines]] [[Category:Hormones of the hypothalamus]] [[Category:Inotropic agents]] [[Category:Neurotransmitters]] [[Category:Phenethylamines]] [[bg:Допамин]] [[ca:Dopamina]] [[cs:Dopamin]] [[da:Dopamin]] [[de:Dopamin]] [[dv:ޑޯޕަމީން]] [[et:Dopamiin]] [[es:Dopamina]] [[fr:Dopamine]] [[ko:도파민]] [[hr:Dopamin]] [[it:Dopamina]] [[he:דופמין]] [[lt:Dopaminas]] [[hu:Dopamin]] [[nl:Dopamine]] [[ja:ドーパミン]] [[no:Dopamin]] [[pl:Dopamina]] [[pt:Dopamina]] [[ru:Дофамин]] [[sl:Dopamin]] [[sr:Допамин]] [[fi:Dopamiini]] [[sv:Dopamin]] [[th:โดพามีน]] [[tr:Dopamin]] [[uk:Дофамін]] [[zh:多巴胺]]