Dopamine: Difference between revisions

{{short description|Organic methchemical butthat nofunctions drugboth as a hormone and a neurotransmitter}}

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

dope, or meth'''Dopamine''' ('''DA''', a contraction of '''3,4-<u>d</u>ihydr<u>o</u>xy<u>p</u>henethyl<u>amine</u>''') is a [[neuromodulatory]] [[molecule]] that plays several important roles in cells. It is an [[organic compound|organic chemical]] of the [[catecholamine]] and [[phenethylamine]] families. Dopamine constitutes about 80% of the catecholamine content in the brain. It is an [[amine]] synthesized by removing a [[carboxyl group]] from a molecule of its [[precursor (chemistry)|precursor chemical]], [[L-DOPA]], which is [[biosynthesis|synthesized]] in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a [[neurotransmitter]]—a chemical released by [[neuron]]s (nerve cells) to send signals to other nerve cells. Neurotransmitters are synthesized in specific regions of the brain, but affect many regions systemically. The brain includes several distinct [[dopaminergic pathway|dopamine pathways]], one of which plays a major role in the motivational component of [[reward system|reward-motivated behavior]]. The anticipation of most types of rewards increases the level of dopamine in the brain,<ref>{{cite journal |vauthors=Berridge KC |date=April 2007 |title=The debate over dopamine's role in reward: the case for incentive salience |journal=Psychopharmacology |language=en-US |volume=191 |issue=3 |pages=391–431 |doi=10.1007/s00213-006-0578-x |pmid=17072591 |s2cid=468204}}</ref> and many [[addiction|addictive]] [[Psychoactive drug|drugs]] increase dopamine release or block its [[reuptake]] into neurons following release.<ref name="Wise2020">{{cite journal |vauthors=Wise RA, Robble MA |date=January 2020 |title=Dopamine and Addiction |journal=Annual Review of Psychology |language=en-US |volume=71 |issue=1 |pages=79–106 |doi=10.1146/annurev-psych-010418-103337 |pmid=31905114 |s2cid=210043316 |doi-access=free}}</ref> Other brain dopamine pathways are involved in [[motor system|motor control]] and in controlling the release of various hormones. These pathways and [[dopaminergic cell groups|cell groups]] form a dopamine system which is [[neuromodulation|neuromodulatory]].<ref name="Wise2020"/>

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 2013 |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 |doi=10.1523/JNEUROSCI.1731-13.2013 |pmc=3792469 |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 2015 |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 |doi=10.1021/cn500255p |pmc=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.}}</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>

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/>