Talk:Dopamine

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DA-mediated cognitive functions

@Looie496: I just went ahead and indicated the VTA projection and target neuron subpopulation that mediates drug reward under Dopamine#Reward. Idk if you're interested in updating the other parts of that section, but I figured I'd just post this here since I'm not particularly keen on updating the entire section myself. This 2014 review^[1] mentions how VTA DA neurons consists of "anatomically and functionally heterogeneous DA subpopulations with different axonal projections" and contains coverage of dopamine-mediated aversion and reward prediction errors. What the review said about distinct neuronal subpopulations/projection targets is something I've read repeatedly about the mesolimbic pathway in particular; the VTA-NAcc pathway contains (at least) 4 distinct subpopulations of projection neurons that synapse onto the D1-type or D2-type MSNs NAcc core or NAcc shell (e.g., see this table), where each of those NAcc subpopulations mediates a distinct function (as noted in the refs I used^[2]^[3]). Seppi333 (Insert 2¢) 21:38, 17 July 2015 (UTC)[reply]

Great, that's fine with me. Looie496 (talk) 21:49, 17 July 2015 (UTC)[reply]

References

^ Lammel S, Lim BK, Malenka RC (2014). "Reward and aversion in a heterogeneous midbrain dopamine system". Neuropharmacology. 76 Pt B: 351–9. doi:10.1016/j.neuropharm.2013.03.019. PMC 3778102. PMID 23578393. An extensive and important body of work subsequently supported the heuristically attractive hypothesis that DA neurons phasic activity encodes reward prediction errors, the discrepancy between an expected reward and the actual outcome. Thus, the omission of an expected reward had the opposite effect on putative DA neuronal activity and silent periods were associated with negative reward prediction errors (Schultz, 1997). The reward prediction error hypothesis has been confirmed in humans using fMRI (D'Ardenne et al., 2008) and more recently using optogenetic single-cell identification of VTA DA neurons in mice (Cohen et al., 2012).
While there is strong evidence in support of the hypothesis that DA neurons signal reward prediction errors, it seems unlikely that this is their only function and that all DA neurons, independent of their projection targets, subserve this single function. Indeed, it is well-established that aversive, stressful and salient events can excite midbrain DA neurons and cause DA release in target structures (Abercrombie et al., 1989; Anstrom and Woodward, 2005; Bassareo et al., 2002; Brischoux et al., 2009; Bromberg-Martin et al., 2010; Cohen et al., 2012; Guarraci and Kapp, 1999; Mantz et al., 1989; Matsumoto and Hikosaka, 2009; Ungless et al., 2010; Young, 2004). However, VTA DA neurons can also be inhibited by aversive stimuli (Mirenowicz and Schultz, 1996; Ungless et al., 2004) and it can be postulated that any increase in DA neuron activity caused by an acute aversive stimulus (e.g. foot shock) might be due to the rewarding effects of terminating the stimulus (Tanimoto et al., 2004). ... An unresolved question is what proportion of DA neurons are excited by aversive stimuli and whether they are a specific subpopulation that project to specific targets.
^ Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues Clin. Neurosci. 15 (4): 431–443. PMC 3898681. PMID 24459410. DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type NAc neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... For example, the shell and core subregions of NAc display differences in drug-induced synaptic plasticity, as do D1- versus D2-type medium spiny neurons within each subregion.^60,63,64,67
^ Dumitriu D, Laplant Q, Grossman YS, Dias C, Janssen WG, Russo SJ, Morrison JH, Nestler EJ (2012). "Subregional, dendritic compartment, and spine subtype specificity in cocaine regulation of dendritic spines in the nucleus accumbens". J. Neurosci. 32 (20): 6957–66. doi:10.1523/JNEUROSCI.5718-11.2012. PMC 3360066. PMID 22593064. The enduring spine density change in core but not shell fits well with the established idea that the shell is preferentially involved in the development of addiction, while the core mediates the long-term execution of learned addiction-related behaviors (Ito et al., 2004; Di Chiara, 2002; Meredith et al., 2008). Consistent with the idea of NAc core being the locus of long-lasting drug-induced neuroplasticity, several studies have shown that electrophysiological changes in core persist longer than their shell counterparts. ... Furthermore, data presented here support the idea that NAc shell is preferentially involved in immediate drug reward, while the core might play a more explicit role in longer-term aspects of addiction.

Feeling of satisfaction

This article is very technical, which is fine I suppose, but I'm having trouble seeing anything in the lede about the effect of satisfaction it has on a person. For instance, if you run a marathon the brain release Dopamine and you get a feeling of extreme satisfaction. Shouldn't this be explained in plain language so the reader can easier identify and understand the overall subject? Jonas Vinther • (Click here to collect your price!) 18:19, 28 July 2015 (UTC)[reply]

That probably isn't even true -- as I understand it, the sense of satisfaction after running a marathon comes largely from the release of endogenous opioids, not dopamine. Anyway, the lede of our article says, "The brain includes several distinct dopamine systems, one of which plays a major role in reward-motivated behavior. Most types of reward increase the level of dopamine in the brain, and a variety of addictive drugs increase dopamine neuronal activity." That seems reasonably clear to me. I agree that the section on the physiology of dopamine does not describe the reward-related effects particularly well, and ought to be improved. Even so, it is never going to be extremely simple, because the unfortunate fact is that the "folk" understanding (i.e., dopamine = pleasure) is not correct. Looie496 (talk) 14:12, 29 July 2015 (UTC)[reply]

I wouldn't discount it entirely; exercise does cause a dopamine efflux because it increases PEA biosynthesis. Seppi333 (Insert 2¢) 16:51, 2 August 2015 (UTC)[reply]

Randomly stumbled across a review - PMID 24133407 - on cognition involving pleasure/hedonic value + reward/motivation in the nucleus accumbens associated with food consumption. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796262/figure/F1/

Food hedonic value appears to be inversely regulated through GLP-1 peptides and their GLP-1 receptor in the NAcc. The review doesn't mention the shell/core + direct/indirect subpopulation of neurons where these are expressed though. Thought this was interesting+worth noting here since I believe the original finding of a distinction between the role for dopamine in reward vs pleasure was based studies with food. I remember reading somewhere that mesolimbic+nigrostriatal lesions decrease motivation for food, but don't affect its hedonic value. Seppi333 (Insert 2¢) 15:14, 13 September 2015 (UTC)[reply]

Drug addiction section

I am thinking about editing this article to a point where it can be nominated for GA and perhaps after that FA. Quite a number of improvements are needed, at many points in the article, but in particular I think the drug addiction section needs a complete reworking. This article is read by a very broad audience, and the drug addiction section is probably one of the parts that will interest readers the most, so I feel that it needs to be made much more accessible. It seems to me that the easiest approach is to go back to the version of 16 March 2014 and then work from there, adding references as needed. A simplified version of the current section could be added as a final paragraph.

To make this easier to evaluate, here is a copy of the version of 16 March 2014:

A variety of addictive drugs produce an increase in reward-related dopamine activity. For some addictive drugs such as alcohol or heroin, activation of the reward system may play only a minor role in addiction, with suppression of suffering being the dominant mechanism, but for other drugs, including nicotine and psychomotor stimulants such as cocaine and methamphetamine, increased postsynaptic dopamine receptor activation or increased levels of synaptic dopamine appear to be the primary factor. When people addicted to stimulants go through withdrawal, they do not experience the physical suffering associated with withdrawal from alcohol or opiates; instead they experience apathy, boredom, restlessness, and most importantly an overwhelming urge to consume more of the drug.^{[medical citation needed]}

The addiction potential for stimulants is strongly dependent on the level of dopamine increase they produce.^{[medical citation needed]}

Treatment of stimulant addiction is very difficult, because even if consumption ceases, the "craving" that comes with psychological withdrawal does not. Even still, when the craving seems to be extinct, it may reemerge when the individual experiences environmental stiumli (friends, locations, situations, etc.) that are associated with the drug. The brain mechanisms underlying these cravings have been a topic of extensive research. There is evidence that they are associated with long-lasting changes in the density of dopamine receptors in parts of the brain.^{[medical citation needed]}

Any thoughts? Looie496 (talk) 15:31, 12 September 2015 (UTC)[reply]

We stopped using the DSM's old definition which grouped addiction and dependence sometime a few months back; we've instead used two sections to cover addiction and dependence–withdrawal separately. Addiction and substance dependence, the {{drugbox}} addiction_liability and dependency_liability parameters, and MOS:MED/MOS:PHARM section guidelines all reflect this distinction, so it would be ideal if this article did too.

As for how to describe addiction... that's a pretty hard problem to tackle. These two reviews (1st is paywalled - linked here temporarily; the 2nd covers addiction in generality, with psychostimulant-specific coverage in certain parts)^[1]^[2] explain addiction in general, describe a subset of the reward system, and describe structure/pathway-specific roles in addiction and addictive behavior. Table 1 in the 1st review contains a list + definitions of addiction-related behavioral terms for context. That review also includes a simplified schematic of the system. Anyway, I'll let you decide how to summarize the disorder, but I'll note that the striatum as a whole is the region of the reward system that drives addiction.

Just for future reference since I figure it's worth mentioning: KEGG has published diagrams on the addiction-inducing signaling cascades of amphetamine, morphine (doesn't show downstream/NAcc signaling, but indicates the DA signaling effect), alcohol, and cocaine (I've seen others in medical literature too). A host of other drugs/drug classes, ~10 of which are listed in the Addiction#Mechanisms section's 1st paragraph, have been shown to signal to the nucleus in the NAcc and overexpress ΔFosB. I don't really have the time/interested to do the same for other drugs as what I did for amphetamine, but I've covered some of this material in several articles (e.g., Ethanol#Addiction). My point is that the current evidence regarding the clinical significance of the NAcc in addiction is often just stated, but rarely explained, in addiction articles on Wikipedia. Seppi333 (Insert 2¢) 18:06, 12 September 2015 (UTC)[reply]

Refs

References

^ Yager LM, Garcia AF, Wunsch AM, Ferguson SM (August 2015). "The ins and outs of the striatum: Role in drug addiction". Neuroscience. 301: 529–541. doi:10.1016/j.neuroscience.2015.06.033. PMID 26116518.
^ Taylor SB, Lewis CR, Olive MF (February 2013). "The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans". Subst. Abuse Rehabil. 4: 29–43. doi:10.2147/SAR.S39684. PMC 3931688. PMID 24648786. The DS (also referred to as the caudate-putamen in primates) is associated with transitions from goal-directed to habitual drug use, due in part to its role in stimulus–response learning.28,46 As described above, the initial rewarding and reinforcing effects of drugs of abuse are mediated by increases in extracellular DA in the NAc shell, and after continued drug use in the NAc core.47,48 After prolonged drug use, drug-associated cues produce increases in extracellular DA levels in the DS and not in the NAc.49 This lends to the notion that a shift in the relative engagement from the ventral to the dorsal striatum underlies the progression from initial, voluntary drug use to habitual and compulsive drug use.28 In addition to DA, recent evidence indicates that glutamatergic transmission in the DS is important for drug-induced adaptations and plasticity within the DS.50{{cite journal}}: CS1 maint: unflagged free DOI (link)

Sources for chemistry and biochemistry sections

Would anybody be able to suggest good references for the chemistry and biochemistry sections? This is textbook-level stuff, and expect the best source is some standard textbook of biochemistry -- I'm sure it won't be found in recent review articles. Unfortunately chemistry is my weak point. I'm reasonably confident that the material in the article is more or less correct, but we can't move to GA or FA if those sections aren't properly referenced. Looie496 (talk) 22:33, 12 September 2015 (UTC)[reply]

If you're asking about structure activity relationships and/or pharmacokinetics, https://books.google.com/books?id=R0W1ErpsQpkC&printsec=frontcover#v=onepage is pretty comprehensive. For chemical-related data on dopamine itself, I'd suggest using pubchem's entry. Seppi333 (Insert 2¢) 04:02, 13 September 2015 (UTC)[reply]

Opiates and ethanol/alcohols

For some addictive drugs such as alcohol or heroin, activation of the reward system may play only a minor role in addiction, with suppression of suffering being the dominant mechanism - ignoring what I wrote/linked above regarding these two drug classes, does the cited ref directly support this clause? Seppi333 (Insert 2¢) 19:54, 21 September 2015 (UTC)[reply]

It definitely supports the first part -- that's basically the theme of the article. (It can be downloaded at http://www.docdroid.net/xk9t/nutt2015.pdf.html if you don't have direct access to it.) It doesn't directly support the second part -- I'll remove that at least until I can locate a clearer source. It's pretty common knowledge though that opiate action and stimulant addiction are quite different in the types of dependence they involve. I'll leave it to you to remove the tag if you think it appropriate.

Let me further say that I hope you feel free to make any edits to this article you think are needed. I just ask that the complexity of the material be kept at a level appropriate for an article that is viewed by thousands of people every day, from a very wide range of backgrounds. Looie496 (talk) 20:56, 21 September 2015 (UTC)[reply]

Seems fine with a minor tweak to the recent revision. Seppi333 (Insert 2¢) 21:07, 21 September 2015 (UTC)[reply]

Lede

The statement "Dopamine is an organic chemical of the catecholamine and phenethylamine families that plays several important roles in the human brain and body, as well as elsewhere in biology" seems to diminish its importance outside humans. The discussion further down the article makes it clear that it is highly conserved and very widespread: found in nearly all multicellular animals. Can we find a more nuanced way of saying this? LeadSongDog come howl! 16:07, 6 October 2015 (UTC)[reply]

I'm open to suggestions. This article gets several thousand page views per day, and I would guess that 80-90% of them come from people mainly interested in the role of dopamine in reward and addiction, so we should make particularly sure the article works for those readers -- but at the same time we shouldn't give an impression that is misleading. Looie496 (talk) 16:16, 6 October 2015 (UTC)[reply]

Perhaps change "the human brain and body" to just "brain and other nerve cells"? LeadSongDog come howl! 04:02, 10 October 2015 (UTC)[reply]

Moving new addition to article here for discussion

The following text was inserted into the "Reward" section by Tasriran (talk · contribs). I am moving here because at best it needs to be discussed; at worst it does not belong. This article is currently a nominee for Featured Article, so it needs to be kept clean while the review proceeds.

Learning from positive and negative information

Studies show that the pharmacological increase of dopamine levels results in a reduction of the ability to learn from negative outcomes^[1] and negative information^[2]. This suggests dopamine plays a role in learning from undesirable outcomes and information.

There are several issues here. (1) The material may be important enough to belong in the article, but it would need to be properly integrated; (2) the references need to be properly formatted (but that's easy enough), (3) the references are primary sources per WP:MEDRS -- we should look for secondary sources, i.e., review articles. Looie496 (talk) 16:30, 6 October 2015 (UTC)[reply]

References

^ Frank, MJ., Seeberger LC., O'reilly, RC. (2004) By carrot or by stick: cognitive reinforcement learning in parkinsonism. Science, Vol 306 (5703) PMID: 15528409
^ Sharot T., Guitart-Masip M., Korn C. W., Chowdhury R., Dolan R.J. (2012) How Dopamine Enhances an Optimism Bias in Humans. Current Biology, Vol 22 (16) doi:10.1016/j.cub.2012.05.053

3D molecular image

Should {{Infobox neurotransmitter}} be modified so we can include a 3D model of the dopamine molecule here? Both {{Drugbox}} and {{Chembox}} have spaces for 2D and 3D models. I'm thinking about this image in particular. Sizeofint (talk) 17:34, 9 October 2015 (UTC)[reply]

Problematic passage in lead

I'm not very happy about this passage: In brain cells, it is transported to synaptic sites and packaged into vesicles for release, which occurs during synaptic transmission. After release, free dopamine is either reabsorbed into the presynaptic terminal for reuse, or broken down by the enzymes monoamine oxidase or COMT, producing a variety of degradation metabolites, whose end products are ultimately excreted in the urine. I can't see any group of readers who benefit from it. To readers who are unfamiliar with neuroscience, it will be completely incomprehensible. To readers who are familiar with neuroscience, the only thing in it that basic knowledge that applies to all neurotransmitters is the names of the metabolizing enzymes. I would like to delete those sentences from the lead, but since they were added by another editor as part of the copy-editing process I don't want to do so without a chance for discussion. Looie496 (talk) 15:13, 8 November 2015 (UTC)[reply]

Agree. I did the bold thing, but others may want to try to rescue some of that content; I think it's best removed, though, for the reasons you gave. What remains is a good intro. — soupvector (talk) 15:47, 8 November 2015 (UTC)[reply]

References in lead

Since there are only two refs given in lead would it be better to remove them. --Iztwoz (talk) 21:12, 17 November 2015 (UTC)[reply]

My general practice is to minimize references in the lead, but not to fight about it if somebody adds one or asks for one. Looie496 (talk) 14:36, 18 November 2015 (UTC)[reply]

Dopamine#Functions

A new review^[1] and IUPHAR both indicate that TAAR1 is a natural/endogenous target of DA along with the 5 DA receptors, so the receptor will need to be included as a target in the "Cellular effects" heading. Given that TAAR1 a high affinity DA receptor, the diagram File:Synapse_dopaminergique.png should probably be revised to include TAAR1 ~~and possibly the inhibitory TAAR1-D2sh heterodimer, which signals through a unique pathway (PKB/GSK3) relative to the individual receptors~~(probably too technical). That's probably the only TAAR1-related material that needs to be added for the comprehensive coverage FA criteria. Seppi333 (Insert 2¢) 04:26, 29 January 2016 (UTC)[reply]

References

^ Grandy DK, Miller GM, Li JX (February 2016). ""TAARgeting Addiction"-The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference". Drug Alcohol Depend. 159: 9–16. doi:10.1016/j.drugalcdep.2015.11.014. PMID 26644139. It also provided the first opportunity to seriously discuss the concept that TAAR1 is a high-affinity receptor for METH/AMPH and DA in the context of a new molecular model of psychostimulant action.
With the focus being on the receptor's role in drug addiction the four speakers presented data that demonstrated to the satisfaction of the audience TAAR1-mediated signaling is activated in vivo by the synthetic psychostimulants METH and AMPH as well as DA, the endogenous trace amines and thyronamines. Furthermore, they showed that selective modulation of TAAR1-mediated signaling using small molecules affects DA D2R-mediated signaling as well as DAT functions with significant consequences in the context of drug-taking and drug-seeking behaviors. ... TAAR1 is a critical component of the greater DA system and as such has to be included in any new model attempting to interpret experimental data related to the neurochemistry of acute and chronic psychostimulant action.

Behavioral Biology of dopamine

There is very little on this page on the role of DA and DA circuits in behavior. Can I create a new section, should there be a new page? Petergstrom (talk) 19:09, 7 December 2016 (UTC)[reply]

The best-studied function is the role of dopamine in reward, which is covered at some length. What kind of material would you like to add? Looie496 (talk) 20:47, 7 December 2016 (UTC)[reply]

Mood, emotion, affect, motor function, and executive function, which are all somewhat covered but not to a crazy extentPetergstrom (talk) 20:54, 7 December 2016 (UTC)[reply]

Well, you're certainly welcome to edit the article, but if you want to add so much material that it would unbalance the presentation it should probably be done in a sub-article. Looie496 (talk) 23:27, 7 December 2016 (UTC)[reply]

It'd probably be best to cover pathway-specific effects in dopaminergic pathways. Seppi333 (Insert 2¢) 03:10, 8 December 2016 (UTC)[reply]

"Prolactin inhibiting hormone"

Since when was dopamine released by an endocrine gland?????Petergstrom (talk) 01:12, 6 January 2017 (UTC)[reply]

As explained in the Nervous system section, "Dopamine produced by neurons in the arcuate nucleus is secreted into the hypophyseal portal system of the median eminence, which supplies the pituitary gland. The prolactin cells that produce prolactin, in the absence of dopamine, secrete prolactin continuously; dopamine inhibits this secretion. In the context of regulating prolactin secretion, dopamine is occasionally called prolactin-inhibiting factor, prolactin-inhibiting hormone, or prolactostatin." Looie496 (talk) 14:40, 8 January 2017 (UTC)[reply]

Also, see this review – Dopamine: a prolactin-inhibiting hormone – and tuberoinfundibular pathway. Seppi333 (Insert 2¢) 16:53, 9 January 2017 (UTC)[reply]

Vasoconstriction vs vasodilation, explanation of revert

An IP editor has changed "vasodilation" to "vasoconstriction" in the lede, explaining with the following edit summary: "Fixed incorrect information: Dopamine is a vassopressor, not a vasodilator, therefore it helps treat low blood pressure in trauma by causing the blood vessels to constrict. This constriction increases vascular resistance which then causes an increase i...". I am about to undo the change, and would like to explain why. This issue has come up before. It's a little tricky: the sources indicate that at normal low biological concentrations, the primary effect of dopamine in the bloodstream is vasodilation. At the much higher concentrations attained when dopamine is injected as a drug, the primary effect becomes vasoconstriction. These effects are covered in the body of the article, citing appropriate sources. Consequently I am going to revert to the earlier version. If there is some tweak to the wording that will make things clearer, I am certainly open to it. Looie496 (talk) 14:33, 8 January 2017 (UTC)[reply]

My Compliments on the Article

My compliments on the article. It comprehensively presents a variety of technical information in a manner that is for the most part highly-readable and begins with the core facts.

One thing is conspicous by its abscence. The production of Dopamine along with other hormones is documented in response to hypoglycaemia. — Preceding unsigned comment added by Leopardtail (talk • contribs) 18:02, 7 August 2017 (UTC)[reply]

Schizophrenia

Looking at the section on pathology, I was surpised to see that schizophrenia was not among the sub-headings. Vorbee (talk) 21:09, 21 November 2017 (UTC) This is especially surprising given that Wikipedia has an article on the dopamine hypothesis of schizophrenia. Vorbee (talk) 21:19, 21 November 2017 (UTC)[reply]

"Basal nuclei"

A recent edit changed "basal ganglia" to "basal nuclei" at several points in this article. The edit has already been reverted, but I think the revert deserves some discussion. (To be clear, I agree with it, but I think there is value in justifying it.) In my opinion, the change to "basal nuclei" is premature. Although that term is logically preferable, it is still far less commonly used in the literature than "basal ganglia". A Google Scholar search from 2017 onward shows over 18,000 uses of "basal ganglia" but only about 800 uses of "basal nuclei", and many of the latter are referring to other things, such as the basal nuclei of the amygdala. The adoption of the term in one textbook is not, in my opinion, sufficient justification for adopting it in Wikipedia. Other opinions are of course welcome. Looie496 (talk) 14:13, 2 June 2018 (UTC)[reply]

Neurotransmitter/hormone

Moved to http://en.wiki.x.io/wiki/Talk:L-DOPA#Dopamine_functions_as_a_neurotransmitter_outside_the_CNS

Evidence of regulating pleasure cognition

Talk:Reward system#Clinical evidence of a causal link between dopamine and music-elicited pleasure - if reproducible, this would result in a paradigm shift in areas of affective neuroscience and cognitive neuropsychology. Seppi333 (Insert 2¢) 01:20, 25 January 2019 (UTC)[reply]

Updated the article with a secondary source. Seppi333 (Insert 2¢) 06:03, 10 August 2019 (UTC)[reply]

"Psychosis and antipsychotic drugs" section, passage removal

I removed the passage:

 "Also, other dissociative drugs, notably ketamine and phencyclidine that act on glutamate NMDA receptors (and not on dopamine receptors) can produce psychotic symptoms.[102]"

Dissociatives do act upon dopamine receptors, both directly and through opioid activity. The source cited originally [102] also backs this up. — Preceding unsigned comment added by 2601:147:4100:6530:D18B:1695:5896:74A7 (talk) 23:04, 13 July 2019 (UTC)[reply]

3-D model is incorrect

Hi, just a quick note to say that the current ball-and-stick model has its upper hydroxy group missing its hydrogen. Thanks, John

No, it is correct - dopamine is a zwitterion in the solid state. See the reference in the image caption: Cruickshank et al., J. Mol. Struct. (2013) 1051, 132-136, which is TIRZAX in the Cambridge Structural Database. The reason dopamine forms this zwitterion is one of the hydroxy groups is so acidic that the amino group takes a proton from it. See also Talk:Adrenaline#Ball_and_stick_model and Norepinephrine for other catecholamines that are zwitterionic for the same treason. Compare them to tyramine that has both zwitterionic and non-zwitterionic forms. And to L-DOPA that is a different kind of zwitterion in which a different OH group is more acidic, the carboxylic OH. --Ben (talk) 11:57, 3 November 2021 (UTC)[reply]

Hi, would you look at my comment below your reply? I apologize in advance for my limited knowledge of chemistry. 69.70.135.194 (talk) 21:36, 2 March 2023 (UTC)[reply]

In this vein the skeletal formula differs from the ball-and-stick model. I think both models should reflect the molecule in the same state (solid or in solution). At the very least it merits a note in the article. — Preceding unsigned comment added by 69.70.135.194 (talk) 21:32, 2 March 2023 (UTC)[reply]

To elaborate, a non-expert reader (like myself) might find the discrepancy confusing. 69.70.135.194 (talk) 21:38, 2 March 2023 (UTC)[reply]

I understand, it is a bit complicated and confusing. I have created a new image based on the previous one but with the solution structure, consistent with the skeletal formula. The solid-state structure is mentioned in the caption. Is this better? Ben (talk) 18:00, 3 March 2023 (UTC)[reply]

History

I can find no evidence of Barger/Ewens synthesising dopamine in the reference Jshake1 (talk) 20:47, 20 September 2023 (UTC)[reply]

Precursor chemical or chemical precursor?

I'm asking for help, because I'm not a native-speaker. "It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical, L-DOPA" Thanks in advance. Retornaire (talk) 18:05, 31 January 2024 (UTC)[reply]

Either seems fine - though I'd be tempted to call it a "molecular precursor" or "precursor molecule". — soupvector (talk) 20:17, 31 January 2024 (UTC)[reply]

[VTA_Reward+Aversion-1] Lammel S, Lim BK, Malenka RC (2014). "Reward and aversion in a heterogeneous midbrain dopamine system". Neuropharmacology. 76 Pt B: 351–9. doi:10.1016/j.neuropharm.2013.03.019. PMC 3778102. PMID 23578393. An extensive and important body of work subsequently supported the heuristically attractive hypothesis that DA neurons phasic activity encodes reward prediction errors, the discrepancy between an expected reward and the actual outcome. Thus, the omission of an expected reward had the opposite effect on putative DA neuronal activity and silent periods were associated with negative reward prediction errors (Schultz, 1997). The reward prediction error hypothesis has been confirmed in humans using fMRI (D'Ardenne et al., 2008) and more recently using optogenetic single-cell identification of VTA DA neurons in mice (Cohen et al., 2012).
While there is strong evidence in support of the hypothesis that DA neurons signal reward prediction errors, it seems unlikely that this is their only function and that all DA neurons, independent of their projection targets, subserve this single function. Indeed, it is well-established that aversive, stressful and salient events can excite midbrain DA neurons and cause DA release in target structures (Abercrombie et al., 1989; Anstrom and Woodward, 2005; Bassareo et al., 2002; Brischoux et al., 2009; Bromberg-Martin et al., 2010; Cohen et al., 2012; Guarraci and Kapp, 1999; Mantz et al., 1989; Matsumoto and Hikosaka, 2009; Ungless et al., 2010; Young, 2004). However, VTA DA neurons can also be inhibited by aversive stimuli (Mirenowicz and Schultz, 1996; Ungless et al., 2004) and it can be postulated that any increase in DA neuron activity caused by an acute aversive stimulus (e.g. foot shock) might be due to the rewarding effects of terminating the stimulus (Tanimoto et al., 2004). ... An unresolved question is what proportion of DA neurons are excited by aversive stimuli and whether they are a specific subpopulation that project to specific targets.

[Cellular_basis-2] Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues Clin. Neurosci. 15 (4): 431–443. PMC 3898681. PMID 24459410. DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type NAc neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... For example, the shell and core subregions of NAc display differences in drug-induced synaptic plasticity, as do D1- versus D2-type medium spiny neurons within each subregion.^60,63,64,67

[Reward_and_the_NAcc_shell_vs_core-3] Dumitriu D, Laplant Q, Grossman YS, Dias C, Janssen WG, Russo SJ, Morrison JH, Nestler EJ (2012). "Subregional, dendritic compartment, and spine subtype specificity in cocaine regulation of dendritic spines in the nucleus accumbens". J. Neurosci. 32 (20): 6957–66. doi:10.1523/JNEUROSCI.5718-11.2012. PMC 3360066. PMID 22593064. The enduring spine density change in core but not shell fits well with the established idea that the shell is preferentially involved in the development of addiction, while the core mediates the long-term execution of learned addiction-related behaviors (Ito et al., 2004; Di Chiara, 2002; Meredith et al., 2008). Consistent with the idea of NAc core being the locus of long-lasting drug-induced neuroplasticity, several studies have shown that electrophysiological changes in core persist longer than their shell counterparts. ... Furthermore, data presented here support the idea that NAc shell is preferentially involved in immediate drug reward, while the core might play a more explicit role in longer-term aspects of addiction.

[Striatal_efferents,_afferents,_and_colocalized_receptors_in_dMSNs_and_iMSNs-4] Yager LM, Garcia AF, Wunsch AM, Ferguson SM (August 2015). "The ins and outs of the striatum: Role in drug addiction". Neuroscience. 301: 529–541. doi:10.1016/j.neuroscience.2015.06.033. PMID 26116518.

[Reward_system_and_psychostimulants-5] Taylor SB, Lewis CR, Olive MF (February 2013). "The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans". Subst. Abuse Rehabil. 4: 29–43. doi:10.2147/SAR.S39684. PMC 3931688. PMID 24648786. The DS (also referred to as the caudate-putamen in primates) is associated with transitions from goal-directed to habitual drug use, due in part to its role in stimulus–response learning.28,46 As described above, the initial rewarding and reinforcing effects of drugs of abuse are mediated by increases in extracellular DA in the NAc shell, and after continued drug use in the NAc core.47,48 After prolonged drug use, drug-associated cues produce increases in extracellular DA levels in the DS and not in the NAc.49 This lends to the notion that a shift in the relative engagement from the ventral to the dorsal striatum underlies the progression from initial, voluntary drug use to habitual and compulsive drug use.28 In addition to DA, recent evidence indicates that glutamatergic transmission in the DS is important for drug-induced adaptations and plasticity within the DS.50{{cite journal}}: CS1 maint: unflagged free DOI (link)

[6] Frank, MJ., Seeberger LC., O'reilly, RC. (2004) By carrot or by stick: cognitive reinforcement learning in parkinsonism. Science, Vol 306 (5703) PMID: 15528409

[7] Sharot T., Guitart-Masip M., Korn C. W., Chowdhury R., Dolan R.J. (2012) How Dopamine Enhances an Optimism Bias in Humans. Current Biology, Vol 22 (16) doi:10.1016/j.cub.2012.05.053

[Miller+Grandy_2016-8] Grandy DK, Miller GM, Li JX (February 2016). ""TAARgeting Addiction"-The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference". Drug Alcohol Depend. 159: 9–16. doi:10.1016/j.drugalcdep.2015.11.014. PMID 26644139. It also provided the first opportunity to seriously discuss the concept that TAAR1 is a high-affinity receptor for METH/AMPH and DA in the context of a new molecular model of psychostimulant action.
With the focus being on the receptor's role in drug addiction the four speakers presented data that demonstrated to the satisfaction of the audience TAAR1-mediated signaling is activated in vivo by the synthetic psychostimulants METH and AMPH as well as DA, the endogenous trace amines and thyronamines. Furthermore, they showed that selective modulation of TAAR1-mediated signaling using small molecules affects DA D2R-mediated signaling as well as DAT functions with significant consequences in the context of drug-taking and drug-seeking behaviors. ... TAAR1 is a critical component of the greater DA system and as such has to be included in any new model attempting to interpret experimental data related to the neurochemistry of acute and chronic psychostimulant action.

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