View source for Dorsal raphe nucleus

{{Infobox brain
| Name            = Dorsal raphe nucleus
| Latin           = nucleus raphes posterior, nucleus raphes dorsalis
| Image           = Drn.png
| Caption         = Outline of the dorsal raphe nucleus: '''DRif''' interfascicular subnucleus, '''DRv''' ventral subnucleus, '''DRvl''' ventrolateral subnucleus, '''DRd''' dorsal subnucleus, '''mlf''' [[medial longitudinal fasciculus]], '''Aq''' [[cerebral aqueduct]], '''IVn''' [[trochlear nucleus]].
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The '''dorsal raphe nucleus''' is one of the [[raphe nuclei]]. It is situated in the [[brainstem]] at the midline. It has rostral and caudal subdivisions:
* The rostral aspect of the ''dorsal'' raphe is further divided into interfascicular, ventral, ventrolateral and dorsal subnuclei.
* The projections of the ''dorsal'' raphe have been found to vary topographically, and thus the subnuclei differ in their projections.<ref>{{cite journal |doi=10.1016/0361-9230(84)90232-6 |vauthors=O'Hearn E, Molliver ME |title=Organization of raphe-cortical projections in rat: a quantitative retrograde study |journal=Brain Res. Bull. |volume=13 |issue=6 |pages=709–26 |date=December 1984 |pmid=6099744 |s2cid=4761755 }}</ref>

== Anatomy ==

=== Efferents ===
The DRN issues serotonergic efferents to the hippocampal formation, limbic lobe, and amygdala (these efferents are involved in regulation of memory processing).<ref name=":1">{{Cite book |last=Patestas |first=Maria A. |title=A Textbook of Neuroanatomy |last2=Gartner |first2=Leslie P. |date= |publisher=Wiley-Blackwell |year=2016 |isbn=978-1-118-67746-9 |edition=2nd |location=Hoboken, New Jersey |pages=432}}</ref>

==Neurophysiology==

=== Serotonergic neurotransmission ===
The dorsal raphe is the largest serotonergic nucleus and provides a substantial proportion of the serotonin innervation to the forebrain.

Serotonergic neurons are found throughout the dorsal raphe nucleus and tend to be larger than other cells.  A substantial population of cells synthesizing [[substance P]] are found in the rostral aspects, many of these co-express serotonin and substance P.  There is also a population of catecholamine synthesizing neurons in the rostral dorsal raphe, and these cells appear to be relatively large.<ref>{{cite journal |vauthors=Baker KG, Halliday GM, Hornung JP, Geffen LB, Cotton RG, Törk I |year=1991 |title=Distribution, morphology and number of monoamine-synthesizing and substance P-containing neurons in the human dorsal raphe nucleus |journal=Neuroscience |volume=42 |issue=3 |pages=757–75 |doi=10.1016/0306-4522(91)90043-N |pmid=1720227 |s2cid=23034680}}</ref>

The dorsal raphe nucleus is rich in [[pre-synaptic]] serotonin [[5-HT1A|5-HT<sub>1A</sub>]] [[autoreceptors]], and it's believed that the action of the [[selective serotonin reuptake inhibitors]] (SSRIs) in this region is responsible for the latency of their antidepressant effect.<ref>{{cite journal |vauthors=Briley M, Moret C |date=October 1993 |title=Neurobiological mechanisms involved in antidepressant therapies |journal=Clin Neuropharmacol |volume=16 |issue=5 |pages=387–400 |doi=10.1097/00002826-199310000-00002 |pmid=8221701}}</ref>

== Research ==

=== Naloxone-induced morphine withdrawal ===
The dorsal raphe nucleus has also been implicated in naloxone-induced morphine withdrawal. It is known that endogenous [[opioid receptors]] exist in the dorsal raphe nucleus, and that it is a focal point as an ascending and descending regulator. Pourshanazari et al. showed in their 2000 paper that electrical stimulation of the dorsal raphe nucleus can partially alleviate [[morphine]] withdrawal symptoms via electrical stimulation of the raphe nucleus in question.<ref>{{cite journal |author=Pourshanazari, A.A.  |author2=Alaei  |author3=Rafati |title=Effects of Electrical Stimulation of Nucleus Raphe Dorsalis on initiation of morphine self-administration in rats |journal=Medical Journal of Islamic Academy of Sciences |volume=13 |issue=2 |pages=63–7 |year=2000}}</ref>

These are fascinating results; however no control was provided for the spread of electrical charge to other parts of the brain stem. It is quite possible that the charge spread to the nucleus raphes magnus and induced [[analgesia]] upon the rats. Knowing that the spread of charge across such a short area is very plausible, as is an alternate connection to the raphe magnus, these results could be called into question.

=== Narcolepsy ===
Wu M.F. ''et al.'' studied the dorsal raphe nucleus as it pertained to [[narcolepsy]]. This is logical, as the raphe nuclei have been known to play a role in the sleep/wake cycle. [[Cataplexy]] is the symptom of narcolepsy when full awareness of the environment is maintained, but all muscle tone is lost. This has thought to be a dissociation of what normally happens during [[Rapid eye movement sleep|REM]] sleep, when all muscle tone is lost except for the eyes. The dorsal raphe nucleus has been known to project to the lateral [[hypothalamus]], along with the [[locus coeruleus]] and the [[tuberomammillary nucleus]]. The neurotransmitters of these three aforementioned nuclei, which project to the lateral hypothalamus, are [[serotonin]], [[norepinephrine]] and [[histamine]] respectively. These neurotransmitters are fully active during waking hours, partially active during non-REM sleep, and have almost ceased during REM sleep. In cats with [[pons|pontine]] lesions, their normal [[atonia]] is not present, the dorsal raphe nucleus is fully active, as opposed to the cessation of action under normal conditions. A muscle relaxant, known as [[Mephenesin]], reduces activity of the dorsal nucleus, as well as microinjections of [[carbachol]] (which induces atonia while awake).<ref>{{cite journal |vauthors=Wu MF, John J, Boehmer LN, Yau D, Nguyen GB, Siegel JM |title=Activity of dorsal raphe cells across the sleep–waking cycle and during cataplexy in narcoleptic dogs |journal=J. Physiol. |volume=554 |issue=Pt 1 |pages=202–15 |date=January 2004 |pmid=14678502 |pmc=1664742 |doi=10.1113/jphysiol.2003.052134 |url=http://www.jphysiol.org/cgi/content/full/554/1/202}}</ref>

=== Depression and suicide ===
The rostral raphe nuclei, both the [[median raphe nucleus]] and particularly the dorsal raphe nucleus have long been implicated in depression. Some studies have suggested that the dorsal raphe may be decreased in size in people with depression and, paradoxically, an increased cell density in those who die by suicide.<ref>{{cite journal |vauthors=Underwood MD, Khaibulina AA, Ellis SP, Moran A, Rice PM, Mann JJ, Arango V
| title = Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims | journal=Biol Psychiatry |volume=46 |issue=4 |pages=473–83 |date=August 1999 |pmid=10459396 |doi=10.1016/S0006-3223(99)00043-8| s2cid = 19780741 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Arango V, Underwood MD, Boldrini M, Tamir H, Kassir SA, Hsiung S, Chen JJ, Mann JJ |title= Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims | journal=Neuropsychopharmacology |volume=25 |issue=6 |pages=892–903 |date=December 2001 |pmid=11750182 |doi=10.1016/S0893-133X(01)00310-4|doi-access=free |hdl=2158/200883 |hdl-access=free }}</ref><ref>{{cite journal |vauthors=Matthews PR, Harrison PJ |title=A morphometric, immunohistochemical, and in situ hybridization study of the dorsal raphe nucleus in major depression, bipolar disorder, schizophrenia, and suicide |journal=J Affect Disord |volume=137 |issue=1–3 |pages=125–134 |date=March 2012 |pmid=22129767 |pmc=3314923 |doi=10.1016/j.jad.2011.10.043}}</ref>

== Other animals ==
An increased number of cells in the lateral aspects of the dorsal raphe is characteristic of primates (including humans).{{Citation needed|date=August 2023}}

=== Rat ===

==== Research ====
Ten percent of the axons from the dorsal raphe nucleus of the rat have been shown to project to the [[amygdala]],<ref>{{cite journal |vauthors=Ma QP, Yin GF, Ai MK, Han JS |date=December 1991 |title=Serotonergic projections from the nucleus raphe dorsalis to the amygdala in the rat |journal=Neurosci. Lett. |volume=134 |issue=1 |pages=21–4 |doi=10.1016/0304-3940(91)90499-J |pmid=1815148 |s2cid=5713957}}</ref> while only medium cells seem to project to the caudate and putamen and olfactory bulb.<ref>{{cite journal |vauthors=Steinbusch HW, Nieuwenhuys R, Verhofstad AA, Van der Kooy D |year=1981 |title=The nucleus raphe dorsalis of the rat and its projection upon the caudatoputamen. A combined cytoarchitectonic, immunohistochemical and retrograde transport study |journal=J. Physiol. (Paris) |volume=77 |issue=2–3 |pages=157–74 |pmid=6169825}}</ref><ref>{{cite journal |vauthors=Petzold GC, Hagiwara A, Murthy VN |date=June 2009 |title=Serotonergic modulation of odor input to the mammalian olfactory bulb |journal=Nat. Neurosci. |volume=12 |issue=6 |pages=784–91 |doi=10.1038/nn.2335 |pmid=19430472 |s2cid=33863055}}</ref>

==See also==
* [[Raphe nuclei]]

==References==
{{Reflist|2}}

==External links==
* [https://www.neuinfo.org/mynif/search.php?q=Dorsal%20Raphe%20Nucleus&t=data&s=cover&b=0&r=20 NIF Search - Dorsal Raphe Nucleus]{{dead link|date=December 2016 |bot=InternetArchiveBot |fix-attempted=yes }} via the [[Neuroscience Information Framework]]

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[[Category:Brainstem nuclei]]
[[Category:Serotonin]]