Dopamine: Difference between revisions

| synonyms = {{ubl|DA, |2-(3,4-Dihydroxyphenyl)ethylamine, |3,4-Dihydroxyphenethylamine, |3-Hydroxytyramine, |Oxytyramine, |Prolactin inhibiting factor, |Prolactin inhibiting hormone,| Intropin,| Revivan}}

| agonists = Direct: [[apomorphine]], [[bromocriptine]]<br/>[[Indirect agonist|Indirect]]: [[cocaine]], [[amphetamine]],[[methylphenidate]]

In [[popular culture]] and media, dopamine is often portrayed as the main chemical of pleasure, but the current opinion in pharmacology is that dopamine instead confers [[motivational salience]];<ref name="NAcc function" /><ref name="pmid24107968">{{cite journal | vauthors = Baliki MN, Mansour A, Baria AT, Huang L, Berger SE, Fields HL, Apkarian AV |date=October title2013 |title= Parceling human accumbens into putative core and shell dissociates encoding of values for reward and pain | journal = The Journal of Neuroscience |language=en-US |volume = 33 | issue = 41 | pages = 16383–93 | date = October 2013 | pmid = 24107968 | pmc = 3792469 | doi = 10.1523/JNEUROSCI.1731-13.2013 |pmc=3792469 quote|pmid=24107968 |quote= <!--Recent evidence indicates that inactivation of D2 receptors, in the indirect striatopallidal pathway in rodents, is necessary for both acquisition and expression of aversive behavior, and direct pathway D1 receptor activation controls reward-based learning (Hikida et al., 2010; Hikida et al., 2013). It seems we can conclude that direct and indirect pathways of the NAc, via D1 and D2 receptors, subserve distinct anticipation and valuation roles in the shell and core of NAc, which is consistent with observations regarding spatial segregation and diversity of responses of midbrain dopaminergic neurons for rewarding and aversive conditions, some encoding motivational value, others motivational salience, each connected with distinct brain networks and having distinct roles in motivational control (Bromberg-Martin et al., 2010; Cohen et al., 2012; Lammel et al., 2013).&nbsp;... Thus, the previous results, coupled with the current observations, imply that the NAc pshell response reflects a prediction/anticipation or salience signal, and the NAc pcore response is a valuation response (reward predictive signal) that signals the negative reinforcement value of cessation of pain (i.e., anticipated analgesia). -->}}</ref><ref name="Aversion neurons">{{cite journal | vauthors = Wenzel JM, Rauscher NA, Cheer JF, Oleson EB |date=January title2015 |title= A role for phasic dopamine release within the nucleus accumbens in encoding aversion: a review of the neurochemical literature | journal = ACS Chemical Neuroscience |language=en-US |volume = 6 | issue = 1 | pages = 16–26 | date = January 2015 | pmid = 25491156 | doi = 10.1021/cn500255p |quotepmc=5820768 |pmid=25491156 |quote=Thus, fear-evoking stimuli are capable of differentially altering phasic dopamine transmission across NAcc subregions. The authors propose that the observed enhancement in NAcc shell dopamine likely reflects general motivational salience, perhaps due to relief from a CS-induced fear state when the US (foot shock) is not delivered. This reasoning is supported by a report from Budygin and colleagues¹¹² showing that, in anesthetized rats, the termination of tail pinch results in augmented dopamine release in the shell.| pmc = 5820768 }}</ref> in other words, dopamine signals the perceived motivational prominence (i.e., the desirability or aversiveness) of an outcome, which in turn propels the organism's behavior toward or away from achieving that outcome.<ref name="Aversion neurons" /><ref name="Motivational salience">{{cite journal | vauthors = Puglisi-Allegra S, Ventura R | title = Prefrontal/accumbal catecholamine system processes high motivational salience | journal = Front. Behav. Neurosci. | volume = 6 | page = 31 | date = June 2012 | pmid = 22754514 | pmc = 3384081 | doi = 10.3389/fnbeh.2012.00031 | quote = <!--Motivational salience regulates the strength of goal seeking, the amount of risk taken, and the energy invested from mild to extreme.&nbsp;... Motivation can be conceptually described as a continuum along which stimuli can either reinforce or punish responses to other stimuli. Behaviorally, stimuli that reinforce are called rewarding and those that punish aversive (Skinner, 1953). Reward and aversion describe the impact a stimulus has on behavior, and provided of motivational properties, thus able to induce attribution of motivational salience.&nbsp;... Attribution of motivational salience is related to the salience of an UCS (Dallman et al., 2003; Pecina et al., 2006). Thus, the more salient an UCS the more likely a neutral (to-be-conditioned) stimulus will be associated with it through motivational salience attribution. Prior experience is a major determinant of the motivational impact of any given stimulus (Borsook et al., 2007) and emotional arousal induced by motivational stimuli increases the attention given to stimuli influencing both the initial perceptual encoding and the consolidation process (Anderson et al., 2006; McGaugh, 2006).-->| doi-access = free }}</ref> It is the [[Cannabinoid|endocannabinoid]], [[2-Arachidonoylglycerol]] (2-AG: [[Carbon|C]]₂₃[[Hydrogen|H]]₃₈[[Oxygen|O]]₄; 20:[[Double bond|4]], [[Omega-6 fatty acid|ω-6]]) that shape [[Nucleus accumbens|accumbal]] encoding of [[Sensory cue|cue]]-[[Motivation|motivated]] behavior via [[Cannabinoid receptor type 1|CB1 receptor]] activation in the [[Ventral tegmental area|ventral tegmentum]], and thereby modulates cue-evoked dopamine transients during the pursuit of [[Reward system|reward]].{{clarification needed|date=November 2023}}<ref>{{cite journal | vauthors = Oleson EB, Beckert MV, Morra JT, Lansink CS, Cachope R, Abdullah RA, Loriaux AL, Schetters D, Pattij T, Roitman MF, Lichtman AH, Cheer JF | display-authors = 6 | title = Endocannabinoids shape accumbal encoding of cue-motivated behavior via CB1 receptor activation in the ventral tegmentum | journal = Neuron | volume = 73 | issue = 2 | pages = 360–373 | date = January 2012 | pmid = 22284189 | pmc = 3269037 | doi = 10.1016/j.neuron.2011.11.018 }}</ref>

Outside the central nervous system, dopamine functions primarily as a local [[paracrine]] messenger. In blood vessels, it inhibits [[norepinephrine]] release and acts as a [[vasodilator]] (at normal concentrations); in the kidneys, it increases sodium excretion and urine output; in the pancreas, it reduces insulin production; in the digestive system, it reduces [[Gastrointestinal physiology#Motility|gastrointestinal motility]] and protects [[intestinal mucosa]]; and in the immune system, it reduces the activity of [[lymphocytes]]. With the exception of the blood vessels, dopamine in each of these peripheral systems is synthesized locally and exerts its effects near the cells that release it.

A dopamine molecule consists of a [[catechol]] structure (a [[benzene]] ring with two [[hydroxyl]] side groups) with one [[amine]] group attached via an [[ethyl group|ethyl]] chain.<ref name="PubChem">{{cite web |title=Dopamine |url=https://pubchem.ncbi.nlm.nih.gov/compound/dopamine |title=Dopamine |publisher=PubChem |access-date=21 September 2015 |publisher=PubChem |language=en-US}}</ref> As such, dopamine is the simplest possible [[catecholamine]], a family that also includes the [[neurotransmitter]]s [[norepinephrine]] and [[epinephrine]].<ref name=Catecholamine>{{cite encyclopedia |url=https://www.britannica.com/science/catecholamine |title=Catecholamine |encyclopedia=Britannica |access-date=21 September 2015}}</ref> The presence of a benzene ring with this amine attachment makes it a [[substituted phenethylamine]], a family that includes numerous [[psychoactive drug]]s.<ref name="Phenethylamine">{{cite web |title=Phenylethylamine |url=http://www.chemicalland21.com/lifescience/phar/PHENYLETHYLAMINE.htm |titleaccess-date=Phenylethylamine21 September 2015 |publisher=ChemicalLand21.com |access-datelanguage=21 September 2015en-US}}</ref>

Like most amines, dopamine is an [[organic base]].<ref name=Carter>{{cite journal |vauthors=Carter JE, Johnson JH, Baaske DM |year=1982 |title=Dopamine Hydrochloride |journal=Analytical Profiles of Drug Substances |volume=11 |pages=257–72|doi=10.1016/S0099-5428(08)60266-X |isbn=978-0122608117 }}</ref> As a [[base (chemistry)|base]], it is generally [[protonation|protonated]] in [[acid]]ic environments (in an [[acid-base reaction]]).<ref name=Carter/> The protonated form is highly water-soluble and relatively stable, but can become [[oxidation|oxidized]] if exposed to oxygen or other [[oxidising agent|oxidants]].<ref name=Carter/> In basic environments, dopamine is not protonated.<ref name=Carter/> In this [[free base]] form, it is less water-soluble and also more highly reactive.<ref name=Carter/> Because of the increased stability and water-solubility of the protonated form, dopamine is supplied for chemical or pharmaceutical use as dopamine [[hydrochloride]]—that is, the [[hydrochloride]] [[salt (chemistry)|salt]] that is created when dopamine is combined with [[hydrochloric acid]].<ref name=Carter/> In dry form, dopamine hydrochloride is a fine powder which is white to yellow in color.<ref>{{Cite web |title=Specification Sheet |url=https://www.sigmaaldrich.com/catalog/DataSheetPage.do?brandKey=SIGMA&symbol=H8502 |titleaccess-date=Specification2019-09-13 Sheet|website=www.sigmaaldrich.com |access-datelanguage=2019en-09-13US}}</ref>

|+[[Biological target|Primary targets]] of dopamine in the human brain<ref name="DA IUPHAR">{{cite web |title=Dopamine: Biological activity | url=http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=940 |access-date=29 January 2016 |website=IUPHAR/BPS guide to pharmacology |publisher=International Union of Basic and Clinical Pharmacology |accesslanguage=en-date=29 January 2016US}}</ref><ref name="Miller+Grandy 2016">{{cite journal | vauthors = Grandy DK, Miller GM, Li JX | title = "TAARgeting Addiction" – The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference | journal = Drug and Alcohol Dependence | volume = 159 | pages = 9–16 | date = February 2016 | pmid = 26644139 | pmc = 4724540 | doi = 10.1016/j.drugalcdep.2015.11.014 | quote = TAAR1 is a high-affinity receptor for METH/AMPH and DA }}</ref>

The substantia nigra is a small midbrain area that forms a component of the [[basal ganglia]]. This has two parts—an input area called the [[pars compactareticulata]] and an output area called the [[pars reticulatacompacta]]. The dopaminergic neurons are found mainly in the pars compacta (cell group A8) and nearby (group A9).<ref name=Bjorklund>{{cite journal | vauthors = Björklund A, Dunnett SB | s2cid = 14239716 | title = Dopamine neuron systems in the brain: an update | journal = Trends in Neurosciences | volume = 30 | issue = 5 | pages = 194–202 | date = May 2007 | pmid = 17408759 | doi = 10.1016/j.tins.2007.03.006 }}</ref> In humans, the projection of dopaminergic neurons from the substantia nigra pars compacta to the dorsal striatum, termed the ''[[nigrostriatal pathway]]'', plays a significant role in the control of motor function and in learning new [[motor skill]]s.<ref name="Malenka pathways" /> These neurons are especially vulnerable to damage, and when a large number of them die, the result is a [[Parkinsonism|parkinsonian syndrome]].<ref>{{cite journal | vauthors = Christine CW, Aminoff MJ | title = Clinical differentiation of parkinsonian syndromes: prognostic and therapeutic relevance | journal = The American Journal of Medicine | volume = 117 | issue = 6 | pages = 412–19 | date = September 2004 | pmid = 15380498 | doi = 10.1016/j.amjmed.2004.03.032 }}</ref>

The arcuate nucleus and the periventricular nucleus of the hypothalamus have dopamine neurons that form an important projection—the ''[[tuberoinfundibular pathway]]'' which goes to the [[pituitary gland]], where it influences the secretion of the hormone [[prolactin]].<ref name=BenJonathan/> Dopamine is the primary [[neuroendocrine]] inhibitor of the secretion of [[prolactin]] from the [[anterior pituitary]] gland.<ref name=BenJonathan/> Dopamine produced by neurons in the arcuate nucleus is secreted into the [[hypophyseal portal system]] of the [[median eminence]], which supplies the [[pituitary gland]].<ref name=BenJonathan/> The [[prolactin cell]]s that produce prolactin, in the absence of dopamine, secrete prolactin continuously; dopamine inhibits this secretion.<ref name=BenJonathan/> In the context of regulating prolactin secretion, dopamine is occasionally called prolactin-inhibiting factor, prolactin-inhibiting hormone, or prolactostatin.<ref name=BenJonathan>{{cite journal | vauthors = Ben-Jonathan N, Hnasko R | title = Dopamine as a prolactin (PRL) inhibitor | journal = Endocrine Reviews | volume = 22 | issue = 6 | pages = 724–63 | date = December 2001 | pmid = 11739329 | doi = 10.1210/er.22.6.724 | doi-access = free }}</ref>

Evidence from [[microelectrode]] recordings from the brains of animals shows that dopamine neurons in the ventral tegmental area (VTA) and substantia nigra are strongly activated by a wide variety of rewarding events.<ref name="Schultz">{{cite journal | vauthors = Schultz W | title = Neuronal Reward and Decision Signals: From Theories to Data | journal = Physiological Reviews | volume = 95 | issue = 3 | pages = 853–951 | date = July 2015 | pmid = 26109341 | pmc = 4491543 | doi = 10.1152/physrev.00023.2014 | quote = <!-- Rewards are crucial objects that induce learning, approach behavior, choices, and emotions. Whereas emotions are difficult to investigate in animals, the learning function is mediated by neuronal reward prediction error signals which implement basic constructs of reinforcement learning theory. These signals are found in dopamine neurons, which emit a global reward signal to striatum and frontal cortex, and in specific neurons in striatum, amygdala, and frontal cortex projecting to select neuronal populations&nbsp;... Figure 12. Reward components inducing the two phasic dopamine response components. The initial component (blue) detects the event before having identified its value. It increases with sensory impact (physical salience), novelty (novelty/surprise salience), generalization to rewarded stimuli, and reward context. This component is coded as temporal event prediction error (389). The second component (red) codes reward value (as reward prediction error)&nbsp;... The salience of rewards derives from three principal factors, namely, their physical intensity and impact (physical salience), their novelty and surprise (novelty/surprise salience), and their general motivational impact shared with punishers (motivational salience). A separate form not included in this scheme, incentive salience, primarily addresses dopamine function in addiction and refers only to approach behavior (as opposed to learning) --> }}</ref> These reward-responsive dopamine neurons in the VTA and substantia nigra are crucial for reward-related cognition and serve as the central component of the reward system.<ref name="NAcc function">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience |vauthors=Malenka yearRC, =Nestler 2009EJ, |Hyman publisherSE |publisher= McGraw-Hill Medical | location year= New York2009 | isbn = 978-0-07-148127-4 |veditors=Sydor pagesA, Brown RY |edition=2nd |location=New York |pages=147–48, 366–67, 375–76 | edition language= 2nden-US | quote= <!-- VTA DA neurons play a critical role in motivation, reward-related behavior (Chapter 15), attention, and multiple forms of memory. This organization of the DA system, wide projection from a limited number of cell bodies, permits coordinated responses to potent new rewards. Thus, acting in diverse terminal fields, dopamine confers motivational salience ("wanting") on the reward itself or associated cues (nucleus accumbens shell region), updates the value placed on different goals in light of this new experience (orbital prefrontal cortex), helps consolidate multiple forms of memory (amygdala and hippocampus), and encodes new motor programs that will facilitate obtaining this reward in the future (nucleus accumbens core region and dorsal striatum). In this example, dopamine modulates the processing of sensorimotor information in diverse neural circuits to maximize the ability of the organism to obtain future rewards.&nbsp;...<br />The brain reward circuitry that is targeted by addictive drugs normally mediates the pleasure and strengthening of behaviors associated with natural reinforcers, such as food, water, and sexual contact. Dopamine neurons in the VTA are activated by food and water, and dopamine release in the NAc is stimulated by the presence of natural reinforcers, such as food, water, or a sexual partner.&nbsp;...<br />The NAc and VTA are central components of the circuitry underlying reward and memory of reward. As previously mentioned, the activity of dopaminergic neurons in the VTA appears to be linked to reward prediction. The NAc is involved in learning associated with reinforcement and the modulation of motoric responses to stimuli that satisfy internal homeostatic needs. The shell of the NAc appears to be particularly important to initial drug actions within reward circuitry; addictive drugs appear to have a greater effect on dopamine release in the shell than in the core of the NAc.&nbsp;... If motivational drive is described in terms of wanting, and hedonic evaluation in terms of liking, it appears that wanting can be dissociated from liking and that dopamine may influence these phenomena differently. Differences between wanting and liking are confirmed in reports by human addicts, who state that their desire for drugs (wanting) increases with continued use even when pleasure (liking) decreases because of tolerance. --><!--&nbsp;... Addictive drugs are rewarding and reinforcing because they act in brain reward pathways to enhance either dopamine release or the effects of dopamine in the NAc or related structures, or because they produce effects similar to dopamine. -->}}</ref><ref name="Hikosaka">{{cite journal | vauthors = Bromberg-Martin ES, Matsumoto M, Hikosaka O | title = Dopamine in motivational control: rewarding, aversive, and alerting | journal = Neuron | volume = 68 | issue = 5 | pages = 815–34 | date = December 2010 | pmid = 21144997 | pmc = 3032992 | doi = 10.1016/j.neuron.2010.11.022 }}</ref><ref name="Striatum">{{cite journal | vauthors = Yager LM, Garcia AF, Wunsch AM, Ferguson SM | title = The ins and outs of the striatum: Role in drug addiction | journal = Neuroscience | volume = 301 | pages = 529–41 | date = August 2015 | pmid = 26116518 | doi = 10.1016/j.neuroscience.2015.06.033 | pmc=4523218}}</ref> The function of dopamine varies in each [[axonal projection]] from the VTA and substantia nigra;<ref name="NAcc function" /> for example, the VTA–[[nucleus accumbens shell]] projection assigns incentive salience ("want") to rewarding stimuli and its associated [[cue reactivity|cues]], the VTA–[[prefrontal cortex]] projection updates the value of different goals in accordance with their incentive salience, the VTA–amygdala and VTA–hippocampus projections mediate the consolidation of reward-related memories, and both the VTA–[[nucleus accumbens core]] and substantia nigra–dorsal striatum pathways are involved in learning motor responses that facilitate the acquisition of rewarding stimuli.<ref name="NAcc function" /><ref name="NAcc core and shell">{{cite journal | vauthors = Saddoris MP, Cacciapaglia F, Wightman RM, Carelli RM | title = Differential Dopamine Release Dynamics in the Nucleus Accumbens Core and Shell Reveal Complementary Signals for Error Prediction and Incentive Motivation | journal = The Journal of Neuroscience | volume = 35 | issue = 33 | pages = 11572–82 | date = August 2015 | pmid = 26290234 | pmc = 4540796 | doi = 10.1523/JNEUROSCI.2344-15.2015 | quote = <!-- Here, we have found that real-time dopamine release within the nucleus accumbens (a primary target of midbrain dopamine neurons) strikingly varies between core and shell subregions. In the core, dopamine dynamics are consistent with learning-based theories (such as reward prediction error) whereas in the shell, dopamine is consistent with motivation-based theories (e.g., incentive salience). --> }}</ref> Some activity within the VTA dopaminergic projections appears to be associated with reward prediction as well.<ref name="NAcc function" /><ref name="NAcc core and shell" />

While dopamine has a central role in causing "wanting," associated with the appetitive or approach behavioral responses to rewarding stimuli, detailed studies have shown that dopamine cannot simply be equated with hedonic "liking" or pleasure, as reflected in the consummatory behavioral response.<ref name=Robinson/> Dopamine neurotransmission is involved in some but not all aspects of pleasure-related cognition, since [[pleasure center]]s have been identified both within the dopamine system (i.e., nucleus accumbens shell) and outside the dopamine system (i.e., [[ventral pallidum]] and [[parabrachial nucleus]]).<ref name=Robinson/><ref name=Berridge2/><ref name="Pleasure system">{{cite journal | vauthors = Berridge KC, Kringelbach ML | title = Pleasure systems in the brain | journal = Neuron | volume = 86 | issue = 3 | pages = 646–64 | date = May 2015 | pmid = 25950633 | pmc = 4425246 | doi = 10.1016/j.neuron.2015.02.018 }}</ref> For example, [[Brain stimulation reward|direct electrical stimulation]] of dopamine pathways, using electrodes implanted in the brain, is experienced as pleasurable, and many types of animals are willing to work to obtain it.<ref name=Wise/> [[Antipsychotic drug]]s reduce dopamine levels and tend to cause [[anhedonia]], a diminished ability to experience pleasure.<ref name="Wise2">{{cite journal | vauthors = Wise RA | title = Dopamine and reward: the anhedonia hypothesis 30 years on | journal = Neurotoxicity Research | volume = 14 | issue = 2–3 | pages = 169–83 | date = October 2008 | pmid = 19073424 | pmc = 3155128 | doi = 10.1007/BF03033808 }}</ref> Many types of pleasurable experiences—such as sexual intercourse, eating, and playing video games—increase dopamine release.<ref name="fn5">{{cite journal |vauthors=Arias-Carrión O, Pöppel E |title=Dopamine, learning and reward-seeking behavior |journal=Acta Neurobiol Exp |volume=67 |issue=4 |pages=481–88 |year=2007|doi=10.55782/ane-2007-1664 |pmid=18320725 |doi-access=free }}</ref> All addictive drugs directly or indirectly affect dopamine neurotransmission in the nucleus accumbens;<ref name="NAcc function" /><ref name=Wise/> these drugs increase drug "wanting", leading to compulsive drug use, when repeatedly taken in high doses, presumably through the [[Addiction#Reward sensitization|sensitization of incentive-salience]].<ref name=Berridge2 /> Drugs that increase synaptic dopamine concentrations include [[psychostimulant]]s such as methamphetamine and cocaine. These produce increases in "wanting" behaviors, but do not greatly alter expressions of pleasure or change levels of satiation.<ref name=Berridge2/><ref name=Wise>{{cite journal | vauthors = Wise RA | title = Addictive drugs and brain stimulation reward | journal = Annual Review of Neuroscience | volume = 19 | pages = 319–40 | year = 1996 | pmid = 8833446 | doi = 10.1146/annurev.ne.19.030196.001535 }}</ref> However, [[opiate]] drugs such as heroin and morphine produce increases in expressions of "liking" and "wanting" behaviors.<ref name=Berridge2/> Moreover, animals in which the ventral tegmental dopamine system has been rendered inactive do not seek food, and will starve to death if left to themselves, but if food is placed in their mouths they will consume it and show expressions indicative of pleasure.<ref>{{cite journal | vauthors = Ikemoto S | title = Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex | journal = Brain Research Reviews | volume = 56 | issue = 1 | pages = 27–78 | date = November 2007 | pmid = 17574681 | pmc = 2134972 | doi = 10.1016/j.brainresrev.2007.05.004 }}</ref>

Parkinson's disease is an age-related disorder characterized by [[movement disorder]]s such as stiffness of the body, slowing of movement, and trembling of limbs when they are not in use.<ref name=Jankovic>{{cite journal | vauthors = Jankovic J | title = Parkinson's disease: clinical features and diagnosis | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 79 | issue = 4 | pages = 368–76 | date = April 2008 | pmid = 18344392 | doi = 10.1136/jnnp.2007.131045 | url = http://jnnp.bmj.com/content/79/4/368.full | doi-access = free }}</ref> In advanced stages it progresses to [[dementia]] and eventually death.<ref name=Jankovic/> The main symptoms are caused by the loss of dopamine-secreting cells in the substantia nigra.<ref name=Dickson>{{cite book | vauthors = Dickson DV|chapter=Neuropathology of movement disorders | veditors = Tolosa E, Jankovic JJ| title=Parkinson's disease and movement disorders |publisher=Lippincott Williams & Wilkins |location=Hagerstown, MD |year=2007 |pages= 271–83 |isbn=978-0-7817-7881-7}}</ref> These dopamine cells are especially vulnerable to damage, and a variety of insults, including [[encephalitis]] (as depicted in the book and movie "''[[Awakenings]]"''), repeated sports-related [[concussion]]s, and some forms of chemical poisoning such as [[MPTP]], can lead to substantial cell loss, producing a [[Parkinsonism|parkinsonian syndrome]] that is similar in its main features to Parkinson's disease.<ref name=Tuite>{{cite journal | vauthors = Tuite PJ, Krawczewski K | title = Parkinsonism: a review-of-systems approach to diagnosis | journal = Seminars in Neurology | volume = 27 | issue = 2 | pages = 113–22 | date = April 2007 | pmid = 17390256 | doi = 10.1055/s-2007-971174 | s2cid = 260319916 }}</ref> Most cases of Parkinson's disease, however, are [[idiopathic]], meaning that the cause of cell death cannot be identified.<ref name=Tuite/>

Many plants, including a variety of food plants, synthesize dopamine to varying degrees.<ref name=Kulma/> The highest concentrations have been observed in bananas—the fruit pulp of [[red banana|red]] and [[Cavendish banana|yellow bananas]] contains dopamine at levels of 40 to 50 parts per million by weight.<ref name=Kulma/> Potatoes, avocados, broccoli, and Brussels sprouts may also contain dopamine at levels of 1 part per million or more; oranges, tomatoes, spinach, beans, and other plants contain measurable concentrations less than 1 part per million.<ref name=Kulma>{{cite journal |vauthors=Kulma A, Szopa J |title=Catecholamines are active compounds in plants |journal=Plant Science |year=2007 |volume=172 |pages=433–40 |doi=10.1016/j.plantsci.2006.10.013 |issue=3|bibcode=2007PlnSc.172..433K }}</ref> The dopamine in plants is synthesized from the amino acid tyrosine, by biochemical mechanisms similar to those that animals use.<ref name=Kulma/> It can be metabolized in a variety of ways, producing [[melanin]] and a variety of [[alkaloid]]s as byproducts.<ref name=Kulma/> The functions of plant catecholamines have not been clearly established, but there is evidence that they play a role in the response to stressors such as bacterial infection, act as growth-promoting factors in some situations, and modify the way that sugars are metabolized. The receptors that mediate these actions have not yet been identified, nor have the intracellular mechanisms that they activate.<ref name=Kulma/>