Wikipedia:Featured article candidates/Dopamine/archive1

The following is an archived discussion of a featured article nomination. Please do not modify it. Subsequent comments should be made on the article's talk page or in Wikipedia talk:Featured article candidates. No further edits should be made to this page.

The article was archived by Graham Beards via FACBot (talk) 11:27, 24 November 2015 [1].

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Dopamine

Nominator(s): Looie496 (talk) 14:25, 3 October 2015 (UTC)

This article is about a substance that plays a very important role in biology; it receives several thousand page views per day. It is currently rated B class, but I've been through the FA process before and I think it's ready for nomination. Let me say a bit about the referencing scheme. The basic concept is that each sentence should cite a reference, with the exception of introductory material that serves only to introduce and summarize material appearing underneath. Thus the lead and several brief introductory paragraphs and introductory sentences don't have refs; they are supported by refs that appear in the following text. There are also a couple of "sky is blue" statements that don't cite sources, but with those exceptions, everything else ought to. I have tried to follow the principles of WP:MEDRS throughout, even though the article is only partly medical. Looie496 (talk) 14:25, 3 October 2015 (UTC)

Comment seems like the diagram for the dopamine pathways is missing the tuberoinfundibular pathway... Mattximus (talk) 22:27, 3 October 2015 (UTC)

It omits a number of minor pathways -- it only shows the largest ones. The caption says "major dopamine pathways", but I suppose that could be further clarified if you think it would be helpful. Looie496 (talk) 01:31, 4 October 2015 (UTC)

Well from the literature there are four major pathways and many minor pathways, and this picture has 3 of the major ones. No biggie, just a comment in passing. Mattximus (talk) 02:37, 6 October 2015 (UTC)

Comments by Chiswick Chap

It's a nicely-organised article and it certainly looks well-cited.

The sections are each on meaty topics and it struck me that many of them ("Attention deficit hyperactivity disorder", "Drug Addiction", "Psychosis", to name but three) deserve a "main" or "further" link. In fact I'd suggest you might go through all the section headings to see if they need such a link, and to add links where needed.

There are inevitably plenty of acronyms. These should be spelt out the first time they occur in the body of the article; ADHD for instance occurs first (not counting the lead) as an acronym. Similarly in the diagrams and captions, for example DAT appears in the "Cocaine increases dopamine levels..." diagram without explanation, whether in the diagram, caption, or even the nearby text; a link would also be helpful.

It might be helpful to wikilink the first occurrences of terms in the image captions. For example, synapse, ventral tegmental area, substantia nigra, striatum, methamphetamine. Chiswick Chap (talk) 15:43, 3 October 2015 (UTC)

Thanks. I don't like to use a "main" when the term appears in the first sentence of a section, but in the cases where it doesn't and seems appropriate I've added one. I have also, as suggested, spelled out acronyms and wikilinked terms in image captions where it wasn't already done. Looie496 (talk) 18:53, 3 October 2015 (UTC)

Questions from John

• In the lead, what does "organic" mean?
• The phrase "a number of" is used seven times in the article. I always find this a very woolly phrase to use, especially on a science article. I am left wondering in each case "What is the number?" Zero is a number, and so is pi, and so is the Avogadro constant. It would usually be better to state the number, or else just say "several" or that the true number is unknown.
• In the lead, the second and fourth paragraphs repeat the information that antipsychotic drugs act by suppressing the effects of dopamine. Saying it once would be fine.

This level of error and infelicity speaks of a lack of copy-editing. If this is how the whole article is written I could not support it on prose. Sorry. --John (talk) 20:51, 4 October 2015 (UTC)

Thanks for the review. Good copy-editing is hard to come by, and more is always welcome. I have wikilinked "organic chemical" -- my initial thought was that it would be overlinking, but I accept your guidance. Regarding "a number of", another editor has kindly reworded all the occurrences of it, but you might consider the possibility that your dislike of it is a personal idiosyncrasy. It is widely used by professional copy editors and even in style guides themselves. I haven't seen any style guide that discourages it. Wikipedia's citation guideline includes the sentence, "A number of organizations have created styles to fit their needs; consequently, a number of different guides exist." Etc. Regarding the repetition, the second paragraph is about diseases, the fourth is about drugs. This fact is crucial in both contexts, and really shouldn't be left out of either paragraph. One possible solution would be to add "As already mentioned above..." or something similar for the second occurrence. I generally dislike that sort of thing, but perhaps it is needed here. Looie496 (talk) 11:45, 5 October 2015 (UTC)

Re "organic chemical"; you missed the point of my question. I will rephrase this. Why is it vital to highlight that the subject is an organic chemical, which substantially just means it is a carbon compound? It is like starting the Adolf Hitler article by stating that the subject was an Austrian vegetarian. Isn't there a more targeted description we could use in the crucial first sentence? --John (talk) 20:46, 16 October 2015 (UTC)

Neurotransmitter is the obvious one, I think. --John (talk) 21:03, 16 October 2015 (UTC)

• In the meantime I oppose the promotion of this article on prose. --John (talk) 10:07, 18 October 2015 (UTC)
• I note with pleasure the input of Cas Liber below. I would be happy to support this after it is reorganised and copyedited a bit as I think all the material is there; it just needs some nips and tucks. --John (talk) 22:28, 27 October 2015 (UTC)

Comment from RexxS

I've done an accessibility check. The table is readable with a screen reader and covers the points in WP:DTT apart from row headers, but the table is small enough for that to not be a concern. The use of colours outside of the images complies with WP:COLOR. The images all have acceptable alt text (now the infobox has been upgraded to take the parameter), although the multiple images in the Chemistry section have captions that repeat the alt text - that could possibly be improved. Three of the images (Synapse dopaminergique.png, Dopamine pathways.svg, Basal ganglia circuits.svg) try to cram too much information into the space they have been allocated and I am unable to read the text. This can be overcome by clicking through to the image page where the text can be read (except for the last one where further zooming is needed to read the black text "Substantia nigra" against a brown background). It's not ideal to force a reader onto another page to read information, but it's not inaccessible. These are relatively minor concerns and should not adversely affect the article's FA candidature. --RexxS (talk) 01:01, 5 October 2015 (UTC)

Thanks. Regarding image sizes, my experience from previous FACs has been that it's usually best to stick with the defaults, but I have no problem with enlarging images if that's the recommendation. Regarding the images in the Chemistry section, I really don't know what else to say there. Looie496 (talk) 11:53, 5 October 2015 (UTC)

Image size is always a judgement call, and sticking with defaults is usually the safest course. It's not your fault that the amount of information in those three images is too much for the default size. In this case, you have to balance the inconvenience of sending the reader off to another page with the potential problems caused by having over-large images taking up a lot of space in the article. You won't please all of the people all of the time. --RexxS (talk) 21:06, 5 October 2015 (UTC)

I wonder if one of our illustration specialists like Evolution and evolvability might be willing to redo File:Synapse_dopaminergique.png? Not only is it hard to read at thumbnail size, it's not very professional-looking. Opabinia regalis (talk) 00:47, 6 October 2015 (UTC)

Redrawing could certainly improve readability. Most of the text labels are very short, and could be increased in size and weight (bolded) without making the diagram larger. Chiswick Chap (talk) 02:41, 6 October 2015 (UTC)

Seppi333 might also be of help, given his experience in similar synapse diagrams. I can't commit to any diagram-making this month, but if it's still in need in November, I can have a go. T.Shafee(Evo﹠Evo)^talk 03:26, 6 October 2015 (UTC)

I suppose I could draw the standard dopamine neurotransmission model if a different image is desired. Main question I'd have though is whether or not it should use {{AI4}} for the labels or just normal text in the image file. If the former is used, the diagram should ideally be large enough so that it can be seen clearly in the article; I'd probably just end up drawing the image so that it's a centered page-spanning (i.e., relatively large width compared to height) diagram anyway though. Seppi333 (Insert 2¢) 14:59, 6 October 2015 (UTC)

• From "Functions", subsection "Storage, release and reuptake", paragraph 3: "Tonic dopamine transmission occurs when small amounts of dopamine are released independently of neuronal activity, and is regulated by the activity of other neurons and neurotransmitter reuptake." If it is regulated by neurons, how is it independent of neuronal activity? Axl ¤ [Talk] 10:49, 7 October 2015 (UTC)

That's one of the few things in the article that I didn't write. I'll look into it. Looie496 (talk) 11:11, 7 October 2015 (UTC)

The intended meaning was that it is independent of neuronal activity in the dopamine-releasing cell, but can be affected by activity in other cells. Even that doesn't quite reflect the source accurately, though -- I've rewritten the whole paragraph in an effort to make it correct and also easier to understand. Looie496 (talk) 12:13, 11 October 2015 (UTC)

Thanks. If several consecutive sentences all use the same reference, there is no need to include the citation at the end of every sentence. You can just include the citation at the end. Axl ¤ [Talk] 10:25, 13 October 2015 (UTC)

• From "Functions", subsection "Nervous system", paragraph 2: "These dopaminergic cell groups were first mapped in 1964 by Annica Dahlström and Kjell Fuxe, who assigned them labels starting with the letter "A" (for "aminergic")." Perhaps move this statement to the "History" section? Axl ¤ [Talk] 10:57, 7 October 2015 (UTC)

It seems useful to me to explain at that point why the dopamine areas are labeled A8-A14. Looie496 (talk) 11:11, 7 October 2015 (UTC)

• From "Functions", subsection "Nervous system": "These neurons are especially vulnerable to damage, and when a large fraction of them die, the result is a Parkinsonian syndrome." More specifically, the result is Parkinson's disease. Axl ¤ [Talk] 11:05, 7 October 2015 (UTC)

No, our Parkinson's disease article explains this. Parkinson's disease is defined as a parkinsonian syndrome that is idiopathic. Looie496 (talk) 11:11, 7 October 2015 (UTC)

I refer you to the second sentence of that very article: "The motor symptoms of Parkinson's disease result from the death of dopamine-generating cells in the substantia nigra." Later, in the "Pathopysiology" subsection: "The primary symptoms of Parkinson's disease result from greatly reduced activity of dopamine-secreting cells caused by cell death in the pars compacta region of the substantia nigra." In this context, "idiopathic" means that the cause of neurone death in the substantia nigra is unknown. Contrast this with, for example, MPTP-induced parkinsonism. Axl ¤ [Talk] 12:10, 7 October 2015 (UTC)

Ah, actually on re-reading the statement, an idiopathic cause is not specified. We can leave statement as it is. Axl ¤ [Talk] 12:28, 7 October 2015 (UTC)

Parkinson's disease#Classification explains the distinction pretty clearly -- or, at least, as clearly as such an obscure thing can be explained. I personally find these distinctions to be annoying pedantry, but people complain if you don't get them right. Looie496 (talk) 12:39, 7 October 2015 (UTC)

• From "Functions", subsection "Basal ganglia", paragraph 1: "The largest and most important sources of dopamine in the vertebrate brain are a pair of structures called the substantia nigra and ventral tegmental area. These two structures are closely related to each other and functionally similar in many respects." There are two areas called the substantia nigra: one on the left and one on the right. The VTA is so close to the midline that it might be reasonable to call the whole thing a single area. It may be better to remove the statement about two/a pair of structures: "The largest and most important sources of dopamine in the vertebrate brain are structures called the substantia nigra and ventral tegmental area. These structures are closely related to each other and functionally similar in many respects." Axl ¤ [Talk] 10:59, 9 October 2015 (UTC)

Okay, I've reworded it so that it no longer talks about "two" structures. Looie496 (talk) 12:36, 9 October 2015 (UTC)

Thanks. Axl ¤ [Talk] 17:37, 9 October 2015 (UTC)

• From "Functions", subsection "Basal ganglia", paragraph 2: "The neural circuitry of the basal ganglia is exceptionally complex." I don't think that "exceptionally" is required. Axl ¤ [Talk] 11:04, 9 October 2015 (UTC)

That might be because you haven't been forced to learn the neural circuitry of the basal ganglia :-). Anyway, I've removed that word. Looie496 (talk) 12:32, 9 October 2015 (UTC)

lol, thank you. Axl ¤ [Talk] 17:37, 9 October 2015 (UTC)

• I wonder if the evidence in "Functions", subsection "Reward", paragraph 1 may be better displayed as a bullet point list? Axl ¤ [Talk] 11:15, 9 October 2015 (UTC)

I usually try to avoid bullet lists, but it does make sense in this case. I've converted it as you suggest. Looie496 (talk) 12:32, 9 October 2015 (UTC)

Thank you. Axl ¤ [Talk] 17:37, 9 October 2015 (UTC)

Comments by Cas Liber

Taking a look now....

as well as elsewhere in biology. - woolly phrase....will think on an alternative

I agree with John about some vague statements that need fine-tuning. Also about duplication. I would try a fix as follows - switch paras 2 and 3 of lead (which gets all physiology in first two paras). Then we have diseases in para 3 and drugs in para 4. As they are now next to each other we can hopefully massage them together.

I'd make a structure section (incorporating the chemistry) section above the Functions section.

The Oxidation section is really about metabolism...in fact, the article needs a metabolism section just below structure and above (or first part of) Functions section. It would also incorporate the biosynthesis and degradation material.

The Polydopamine segment would go in a History and uses section I think.

sorry about the gross scope of suggestions but I think the article needs a major reorganisation of content (as detailed above). Good luck and let me know if you want me to do that. Once done will keep reading. Cas Liber (talk · contribs) 13:08, 26 October 2015 (UTC)

Thanks for the review. An important point here is that this article is viewed by several thousand people each day, and I'm sure the great majority of them are looking for information about one of three things: the role of dopamine in reward; the role of dopamine in addiction; the role of dopamine in schizophrenia. I'm concerned that the reorganization you advocate would bury that material so deeply that readers would never get to it. Many other encyclopedic treatments of dopamine focus almost exclusively on the three aspects I listed, and simply leave out the other stuff. Looie496 (talk) 13:46, 26 October 2015 (UTC)

Errr, the first bit I am talking about is the lead, which is not of a length that anything gets buried in it. The other is a way of coherently organising the information about the subject so it is discussed in a structured way. The structure and then the metabolism should come before the functions as the first two are building blocks for the third. Hence we do not have a logical topic flow as is. Both sections I want to put above are short, so I would disagree that the "functions" bit is going to get buried. Don't forget it's also touched on in the lead. By all means wait for some other science-medicine types to comment and we can see where consensus lies. Cas Liber (talk · contribs) 01:23, 27 October 2015 (UTC)

I didn't mean to argue about what you said about the lead. Anyway, I'm willing for you to reorganize the article as you see fit, if you'd like to give that a try. My general sense is that articles should be front-loaded with the parts that are most interesting to readers, and functional aspects are always more interesting than structural aspects, but I'm open to being persuaded by the result. Looie496 (talk) 11:37, 27 October 2015 (UTC)

I am happy for anyone to express an opinion different to me (and would rather they do that than suffer in silence or fell like they are being held to ransom here). I will have a go at a rejig in the next few hours. Cas Liber (talk · contribs) 23:48, 27 October 2015 (UTC)

• Update - have done this, which I think is the logical flow. Need to loook at sections to check for duplication and flow (and missing stuff). Will do so and have a think. Cas Liber (talk · contribs) 23:56, 27 October 2015 (UTC)

• Update - have threaded info on conditions and their treatment thus to reduce repetition and consolidate as the cause and treatment rationales are tightly linked and make more sense (to me that is) to be placed next to each other WRT each condition.

*Update - am okay with prose and structure now...just need to review content, comprehensiveness and weighting. Cas Liber (talk · contribs) 20:02, 5 November 2015 (UTC)

I'd remove the second sentence in Antipsychotic drugs section - somewhat outdated and not necessary for context here. did it myself

Once that sentence is removed, this one (The most prominent effect of these drugs is to reduce the activity of dopamine systems, mainly by antagonizing D2 receptors) can be split in half with the repetitive bit removed and the mention of D2 tacked onto the first sentence did it myself

Antipsychotic drugs have a broadly suppressive effect on most types of active behavior, and particularly reduce the delusional and agitated behavior characteristic of overt psychosis - is not strictly true. Many are non sedating and aripiprazole is decidedly activating.....

I think the antipsychotic section needs to focus more on the receptors rather than the benefit - more specifically about which ones they work on. aripiprazole is a partial dopamine agonist, and hence its action belongs squarely in this article. Amisulpride is a D2 and D3 antagonist, and hence deserves mention as acting on different receptors. Am tempted to put something about "atypicals" (the division between typicals and atypicals is horseshit anyway for the most part) and serotonin as a footnote. e.g. risperidone's activity is more anti serotonergic. I will have a tinker with this section later today.

The more I look at it the more I think we could dispense with the whole second para - or at the very least swap the third with second para.

In the following decades other types of antipsychotic drugs with fewer serious side-effects were developed - I'd want a better source than someone's opinion (even Healy's!), drug companies have consistently pushed this line which has been disputed.

• I tend to think that disease processes should come before treatments...and wonder whether combining disease processes and treatments somehow to prevent reduplication....

Comments from Mike Christie

I'll add comments here as I go through the article. It might take me a day or two to complete the review. I'm not knowledgeable about the topic area, so this will be a review from a lay perspective. I'll copyedit as I go; please revert if I mess anything up.

• Why is "paracrine" in quotes in the lead? If it requires glossing, wouldn't it be better to avoid using the word in the lead, and just give the meaning?
  • Done as suggested. Looie496 (talk) 12:56, 28 October 2015 (UTC)
• "Several important diseases of the nervous system are associated with dysfunctions of the dopamine system, some of the key medications used to treat them involve altering metabolism of the hormone." This is a run-on sentence, so I've changed it to a colon instead of a comma in the middle. However, I also noticed that "the hormone" is used, but you haven't said up to this point that dopamine is a hormone. Although it's a little repetitive, I think this would be better as "altering dopamine metabolism".
  • That sentence was a result of Casliber's merger of what were previously two sentences from different paragraphs. I have reworded it to hopefully reduce the awkwardness. Looie496 (talk) 13:02, 28 October 2015 (UTC)

    Tweaked. Mike Christie (talk - contribs - library) 00:20, 29 October 2015 (UTC)

• "Its metabolic precursor L-DOPA is the most widely used treatment for the condition": "It" refers to dopamine, but the preceding sentence doesn't have "dopamine" in a way that makes it a referent for "it" here. I'd suggest something like "L-DOPA, the metabolic precursor of dopamine, is the most widely used treatment for the condition".
  • I actually wrote it the way you suggest, and Casliber copy-edited it to its current form. I wouldn't like to change it back without agreement from him. Looie496 (talk) 13:23, 28 October 2015 (UTC)

    Cas, can you comment? I think it's not ideal as it stands. Mike Christie (talk - contribs - library) 00:20, 29 October 2015 (UTC)

    • @Mike Christie: you guys are right in that it needs to be reworded, the suggestion above is a good one. (sorry, missed this) Cas Liber (talk · contribs) 19:35, 5 November 2015 (UTC)

• I don't think you need the bullet at the start of the metabolic pathway in the "Synthesis" section.
  • I have removed it. Looie496 (talk) 13:23, 28 October 2015 (UTC)
• Not an issue for this article, but I'm curious: is there a reason why File:L-DOPA-to-dopamine.svg shows the ethylamine chain moving from one carbon atom to the next in the L-DOPA -> dopamine reaction? Because of symmetry, there's no actual difference between those two locations (or so I would assume), so perhaps it's just the conventional way each molecule is drawn.
  • I don't actually know anything about this. I took that picture from Commons. Chemistry is my weakest point, and for anything subtle I have to rely on what other people tell me. Looie496 (talk) 13:23, 28 October 2015 (UTC)

    Struck, since it's not relevant here; I might ask at the chemistry WikiProject. Mike Christie (talk - contribs - library) 00:20, 29 October 2015 (UTC)

• "this mechanism may contribute to cell loss that occurs in Parkinson's disease or other conditions": suggest "this mechanism may contribute to the cell loss that occurs in Parkinson's disease and other conditions". Using "or" seems incorrect to me, since the cell loss doesn't occur in one disease *or* the other; it occurs in both.
  • I have changed the wording as you suggest. Looie496 (talk) 13:23, 28 October 2015 (UTC)
• Why the upper-case initial letter in "Vanillylmandelic acid"?
  • Actually this was an error on my part -- VMA is very slightly different from HVA, so I have simply removed the mention of it. Looie496 (talk) 13:23, 28 October 2015 (UTC)
• What's the difference between the "metabolism" and "degradation" sections? They seem to be saying the same thing in different ways.
  • This was a result of Casliber's reorganization. I have merged the two, with a bit of rewording to make them fit together. Looie496 (talk) 13:23, 28 October 2015 (UTC)

-- More later. Mike Christie (talk - contribs - library) 11:58, 28 October 2015 (UTC)

Continuing the review:

• "basic lower-level functions": what's the difference in meaning between "basic" and "lower-level"?
  • I have removed "basic", which I agree was redundant here. Looie496 (talk) 14:30, 30 October 2015 (UTC)
• "they send projections to many other brain areas": I'm not sure what this means. Do you mean that these neurons have axons (if I have the terminology right) that extend to the other brain areas? If so, can we be more direct? I see from later in the article that the word "projection" may have this specific meaning in neurology, in which case perhaps a link or a gloss in a footnote would be enough.
  • I changed it to "but their axons project to many other brain areas, and they exert powerful effects on their targets". That's a bit awkward, but I doubt there is a perfect solution here. Looie496 (talk) 14:30, 30 October 2015 (UTC)

    I think using "projection" with an explanatory footnote would have been OK too, since you use "projection" later in the article, but this is fine. Mike Christie (talk - contribs - library) 13:09, 31 October 2015 (UTC)

• "The neural circuitry of the basal ganglia is complex, and progress in understanding their functions has been slow": surely "its functions", since "circuitry" is singular here?
  • My intent was for the pronoun to refer to "basal ganglia", which is plural. To avoid confusion I simplified the whole sentence, so now it reads, "Progress in understanding the functions of the basal ganglia has been slow.". Looie496 (talk) 14:30, 30 October 2015 (UTC)
• "neurochemists have also developed a variety of research drugs that bind with high affinity to specific types of dopamine receptors and agonize or antagonize their effects, plus a variety that affect other aspects of dopamine physiology": to avoid two uses of "variety", how about making this "neurochemists have also developed a variety of research drugs, some of which bind with high affinity to specific types of dopamine receptors and agonize or antagonize their effects, and others that affect other aspects of dopamine physiology"? Or "some of which affect other aspects"?
  • Reworded as "developed a variety of research drugs, some of which bind with high affinity to specific types of dopamine receptors and agonize or antagonize their effects, and many that affect other aspects of dopamine physiology". Looie496 (talk) 14:30, 30 October 2015 (UTC)
• "A separate dopamine-producing population of cells appears to increase aversion learning of olfactory cues, much like in mammals": the "Animals" section doesn't mention this, or indeed any other, fact about mammals, or any vertebrate. Any reason for the exclusion?
  • Sorry, I didn't write that and didn't pay enough attention to it. I have simply deleted that sentence, which doesn't say anything essential. Looie496 (talk) 14:30, 30 October 2015 (UTC)
• In the first paragraph of "History and development", I'd suggest using underlining or bolding rather than italics to pick out the letters; the italic "o" in particular is very hard to see.
  • I changed them to bold. It looks a little weird but is definitely easier to see. Looie496 (talk) 14:30, 30 October 2015 (UTC)

-- I'm done with a first pass. The article is in excellent shape; I found it very readable. I expect to support once the minor points above are dealt with. Mike Christie (talk - contribs - library) 02:34, 29 October 2015 (UTC)

Support. There's one comment unstruck; if Cas doesn't respond to the question I asked I will raise it on the article talk page after the FAC is over, but it's a minor point. I saw John's comments above about prose -- I think the prose is now in good shape. I like the article structure. I can't speak to comprehensiveness, but I don't see any obvious omissions in coverage. This is a fine article. Mike Christie (talk - contribs - library) 13:25, 31 October 2015 (UTC)

support per:[2]--Ozzie10aaaa (talk) 08:26, 7 November 2015 (UTC)

• article is (well written,researched, stable, neutral, comprehensive)-major pathways are ok
• style (lead, structure, citations)
• media -images should be default,though a couple have significant text/caption
• length

Comment the stoichiometry of the reaction in the version that was displayed is incorrect - there is no need for the proton (H⁺) as input, because L-DOPA and dopamine both have 11 hydrogen atoms. I'll edit the image on Commons to remove the proton addition. — soupvector (talk) 20:38, 7 November 2015 (UTC)

I've also flipped dopamine vertically to make the synthesis clearer. — soupvector (talk) 20:44, 7 November 2015 (UTC)

Comments by delldot

Generally pretty great! This is mostly just a pile of minor prose tweaks:

• Any way to incorporate "neuromodulation" into the text and eliminate the See also section with one link?
  • I dislike that term because I feel it's a buzzword that doesn't actually promote understanding -- I left it there because it was added by another editor, but I'm reluctant to use it. If it was used in the text it would need to be explained, and that would be a distraction. Looie496 (talk) 15:19, 11 November 2015 (UTC)
    • Ooh, I just hate teeny see also sections is all. Oh well, it's such a minor thing anyway. delldot ∇. 17:19, 11 November 2015 (UTC)

• compensating for peripheral dopamine metabolism -> would it be clearer to say compensating for dopamine metabolism elsewhere in the body or something?
  • Changed to "compensating for dopamine metabolism that occurs outside the nervous system". Looie496 (talk) 15:19, 11 November 2015 (UTC)

• This 'it' is a little unclear: The ability of dopamine autoxidation to produce quinones and free radicals makes it a potent cell toxin. Could you say, these breakdown products make dopamine a potent cell toxin? Or Since its autoxidation produces quinones and free radicals, dopamine is a potent cell toxin?
  • The wording here has been changed by another editor. Is it okay now? Looie496 (talk) 15:19, 11 November 2015 (UTC)
    • Great. delldot ∇. 17:19, 11 November 2015 (UTC)

• I would rearrange this sentence: Dopamine is stored in these vesicles until it is ejected into the synaptic cleft, typically after an action potential causes the vesicles to release their contents directly into the synaptic cleft through a process called exocytosis, but also sometimes as a result of mechanisms that do not require action potentials Dopamine is stored in these vesicles until it is ejected into the synaptic cleft, when vesicles release their contents through a process called exocytosis. This is typically caused by an action potential, but also sometimes as a result of mechanisms that do not require action potentials. Or you could drop the action potential part since that's discussed in the phasic/tonic para below.
  • I have reworded it: "Dopamine is stored in these vesicles until it is ejected into the synaptic cleft through a process called exocytosis. In most cases exocytosis is caused by action potentials, but it can also be caused by mechanisms that do not require neural activity". Looie496 (talk) 15:19, 11 November 2015 (UTC)

• They are then absorbed back into the presynaptic cell, via reuptake mediated either by the high-affinity dopamine transporter or by the low-affinity plasma membrane monoamine transporter. Should the reader be expected to know what affinity is, or should that be explained?
  • I have removed "high-affinity" and "low-affinity". Looie496 (talk) 17:21, 11 November 2015 (UTC)

• This sentence could be broken up into a few smaller ones: Dopaminergic neurons (i.e., neurons whose primary neurotransmitter is dopamine) are comparatively few in number—a total of around 400,000 in the human brain[19]—and their cell bodies are confined to a few relatively small brain areas, but their axons project to many other brain areas, and they exert powerful effects on their targets.
  • I can't see how to improve it that way, but if you would like to, please feel free to edit it. Looie496 (talk) 17:21, 11 November 2015 (UTC)
    • I just made it ... their cell bodies are confined to a few relatively small brain areas.[20] However their axons project to many other brain areas...[20] delldot ∇. 23:01, 11 November 2015 (UTC)

• This sentence seems like a non-sequitur, and it's not clear why it's important: The name substantia nigra is Latin for "black substance", and refers to the fact that the dopaminergic neurons there are darkly pigmented. Also if it were removed the previous and following sentences about motor function would flow better.
  • I thought it would be interesting to readers, but per your recommendation I have removed it. You are certainly right about the flow. Looie496 (talk) 17:21, 11 November 2015 (UTC)
    • It's mentioned again below, so could add info there. delldot ∇. 22:52, 11 November 2015 (UTC)

• Repitition of 'greatly reduced': Parkinson's disease, in which dopamine levels in the substantia nigra circuit are greatly reduced, is characterized by stiffness and greatly reduced movement.
  • I changed "greatly reduced movement" to "difficulty initiating movement". Looie496 (talk) 17:21, 11 November 2015 (UTC)

My main concern throughout the article is it's unclear whether a section is talking just about humans or about all mammals or other animals. e.g. in the reward section bulleted list, some items are just about people and some about animals. I think a lot of these instances could be clarified with footnotes, or just by beginning a sentence or para with 'In humans,' or 'In mammals', or whatever.

The challenge is to to that without awkwardness. In the bullet list, I believe the facts stated there are valid for humans and other mammals, but the techniques used to obtain evidence may only be usable in one or the other. For example microelectrode brain recordings can generally only be obtained from animals (for ethical reasons), but if they were done on humans they would almost certainly give the same results. In any case I'm open to clarifying this if you point to specific instance that seem problematic. Looie496 (talk) 17:21, 11 November 2015 (UTC)

Anyway, I thought I'd give you a chance to respond to those, then I'll come back with more comments later. delldot ∇. 19:08, 10 November 2015 (UTC)

Cool, thanks for the review. Looie496 (talk) 17:21, 11 November 2015 (UTC)

Here are my thoughts about the rest of the article:

• Like cocaine, substituted amphetamines increase the concentration of dopamine in the synaptic cleft, but by a different mechanism, involving complex intracellular effects.[17] MDMA also increases dopamine levels by a complex combination of mechanisms. Could these sentences be combined? e.g. Like cocaine, substituted amphetamines[17] and MDMA increase the concentration of dopamine in the synaptic cleft, but by different mechanisms, involving complex intracellular effects.[62]:147–150
  • I have combined the two as you suggest, but left out the last clause, which I don't think is really needed. Looie496 (talk) 17:43, 16 November 2015 (UTC)

• This rapid and brief action gives it high addiction potential. Could there be a brief explanation for why this is?

  Response to this could cite a recent review (PMID 26116543) which notes in the abstract, Rapid drug onset and intermittent drug exposure both appear to push the addiction process forward most effectively. — soupvector (talk) 01:44, 16 November 2015 (UTC)

  • I reworded the sentence to say, "This rapid and brief action makes its effects easy to perceive and consequently gives it high addiction potential." A longer explanation would be a distraction here. Looie496 (talk) 17:43, 16 November 2015 (UTC)
    • Yeah, that's perfect. delldot ∇. 18:15, 17 November 2015 (UTC)

• Seems like the pain subseccction could use some fleshing out. It says, Dopamine plays a role in pain processing in [all these areas], is it possiblle to be more specific about what the role is? Or what areas are involved in the phenomena in the next two sentences?
  • It might be that the best response is to delete that section. I don't have access to the source article used to justify it (the abstract supports the statements in the Wikipedia article). I expect I can get it, but I'm not sure this topic has enough weight to justify it. All of the detail I know of comes from primary sources. Looie496 (talk) 17:43, 16 November 2015 (UTC)
    • I was able to get the article, so email me if you want it. I don't know whether this role is well established enough to merit its own section, I'll have to leave that to others to decide. If you delete it maybe you could just put a sentence in the first para of the Disease, disorders, and pharmacology section (or somewhere) to the effect of "research also suggests that it plays a role in pain processing." delldot ∇. 18:15, 17 November 2015 (UTC)

• The lead doesn't really mention its roles in other life forms. Do you think something like this deserves a mention? Dopamine is used as an intercellular messenger in virtually all multicellular animals.

• The para beginning Dopamine consumed in food cannot act on the brain, because it cannot cross the blood–brain barrier talks about foods with L-DOPA that can cross it, but doesn't say what the effect is when people eat it. Are there any more details? If the L-DOPA-containing foods also have no effect, is it accurate to say the dopamine foods cannot act on the brain because it cannot cross the blood–brain barrier?
  • This is tricky. When L-DOPA is administered as a drug, over 90% is converted to dopamine outside the nervous system unless adjunct drugs (carboxylase inhibitors) are co-administered to prevent that. One would expect the same thing to happen with L-DOPA that is eaten. Even so, some dopamine would be expected to be generated in the nervous system -- but enough to make a difference? I'm not aware of any research that has directly examined the question. There is a widespread belief that eating fava beans increases brain dopamine, but as far as I know there is no direct evidence to support it. This whole topic has a pretty minimal literature. Looie496 (talk) 17:43, 16 November 2015 (UTC)
    • I wonder if you could find a source that backs up something like "little is known about what if any effect eating foods that contain L-DOPA has". You see what I mean about how this para the way it is kind of leaves you hanging, right? "Dopamine-containing foods have no effect because dopamine can't cross the BBB. But these foods have L-DOPA, which can cross it." It's like dot dot dot... delldot ∇. 18:15, 17 November 2015 (UTC)

• Would it make sense to move the green algae para to before the foods para? Then it would flow like, list of different roles in plants, role in algae for defense because of dopamine's effect on animals, (lack of) effects on the human brain. Also, is there any info on what the algae dopamine does to the snails to keep them from eating it?
  • The algae business seems too interesting to leave out, but I don't want to give it too much emphasis because (a) all of the information comes from primary sources, and (b) as far as the literature shows the use of dopamine in this way is unique to this one particular species of algae. The mechanism by which dopamine deters eating has not been determined. Looie496 (talk) 17:43, 16 November 2015 (UTC)

Let me know what you think! delldot ∇. 00:31, 16 November 2015 (UTC)

Closing comment - This FAC nomination has been open a long time but a clear consensus to promote the article to FA has not been reached. I have decided to archive this lengthy FAC and encourage the nominator to address any remaining issues (on the article's Talk Page if necessary) and re-nominate the article after the standard two-weeks from closing. Graham Beards (talk) 11:27, 24 November 2015 (UTC)

• Closing note: This candidate has been archived, but there may be a delay in bot processing of the close. Please see WP:FAC/ar, and leave the {{featured article candidates}} template in place on the talk page until the bot goes through.Graham Beards (talk) 11:27, 24 November 2015 (UTC)

The above discussion is preserved as an archive. Please do not modify it. No further edits should be made to this page.