Editing Serotonin (section)

=== Vertebrates ===
Serotonin, also referred to as 5-hydroxytryptamine (5-HT), is a neurotransmitter most known for its involvement in mood disorders in humans. It is also a widely present neuromodulator among vertebrates and invertebrates.<ref name="Bacqué-Cazenave_2020">{{cite journal | vauthors = Bacqué-Cazenave J, Bharatiya R, Barrière G, Delbecque JP, Bouguiyoud N, Di Giovanni G, Cattaert D, De Deurwaerdère P | title = Serotonin in Animal Cognition and Behavior | journal = International Journal of Molecular Sciences | volume = 21 | issue = 5 | pages = 1649 | date = February 2020 | pmid = 32121267 | pmc = 7084567 | doi = 10.3390/ijms21051649 | doi-access = free }}</ref> Serotonin has been found having associations with many physiological systems such as cardiovascular, [[thermoregulation]], and behavioral functions, including: [[circadian rhythm]], appetite, aggressive and sexual behavior, sensorimotor reactivity and learning, and pain sensitivity.<ref name="Lucki_1998">{{cite journal | vauthors = Lucki I | title = The spectrum of behaviors influenced by serotonin | journal = Biological Psychiatry | volume = 44 | issue = 3 | pages = 151–162 | date = August 1998 | pmid = 9693387 | doi = 10.1016/s0006-3223(98)00139-5 | s2cid = 3001666 | doi-access = free }}</ref> Serotonin's function in neurological systems along with specific behaviors among vertebrates found to be strongly associated with serotonin will be further discussed. Two relevant case studies are also mentioned regarding serotonin development involving [[Teleost|teleost fish]] and [[Mouse|mice]].

In mammals, 5-HT is highly concentrated in the [[substantia nigra]], [[ventral tegmental area]] and [[raphe nuclei]]. Lesser concentrated areas include other brain regions and the spinal cord.<ref name="Bacqué-Cazenave_2020" /> 5-HT neurons are also shown to be highly branched, indicating that they are structurally prominent for influencing multiple areas of the [[Central nervous system|CNS]] at the same time, although this trend is exclusive solely to mammals.<ref name="Lucki_1998" />

====5-HT system in vertebrates====
[[Vertebrate]]s are multicellular organisms in the [[Chordate|phylum Chordata]] that possess a backbone and a [[nervous system]]. This includes mammals, fish, reptiles, birds, etc. In humans, the nervous system is composed of the [[Central nervous system|central]] and [[peripheral nervous system]], with little known about the specific mechanisms of neurotransmitters in most other vertebrates. However, it is known that while serotonin is involved in stress and behavioral responses, it is also important in [[cognitive functions]].<ref name="Bacqué-Cazenave_2020" /> Brain organization in most vertebrates includes 5-HT cells in the [[hindbrain]].<ref name="Bacqué-Cazenave_2020" /> In addition to this, 5-HT is often found in other sections of the brain in non-placental vertebrates, including the [[basal forebrain]] and [[Pretectal area|pretectum]].<ref name="Backström_2017">{{cite journal | vauthors = Backström T, Winberg S | title = Serotonin Coordinates Responses to Social Stress-What We Can Learn from Fish | journal = Frontiers in Neuroscience | volume = 11 | pages = 595 | date = 2017-10-25 | pmid = 29163002 | pmc = 5669303 | doi = 10.3389/fnins.2017.00595 | doi-access = free }}</ref> Since location of serotonin receptors contribute to behavioral responses, this suggests serotonin is part of specific pathways in non-placental vertebrates that are not present in amniotic organisms.<ref>{{cite journal | vauthors = Berger M, Gray JA, Roth BL | title = The expanded biology of serotonin | journal = Annual Review of Medicine | volume = 60 | issue = 1 | pages = 355–366 | date = 2009-02-01 | pmid = 19630576 | pmc = 5864293 | doi = 10.1146/annurev.med.60.042307.110802 }}</ref> Teleost fish and mice are organisms most often used to study the connection between serotonin and vertebrate behavior. Both organisms show similarities in the effect of serotonin on behavior, but differ in the mechanism in which the responses occur.

=====Dogs / canine species=====
There are few studies of serotonin in dogs. One study reported serotonin values were higher at dawn than at dusk.<ref>{{cite journal | vauthors = Alberghina D, Piccione G, Pumilia G, Gioè M, Rizzo M, Raffo P, Panzera M | title = Daily fluctuation of urine serotonin and cortisol in healthy shelter dogs and influence of intraspecific social exposure | journal = Physiology & Behavior | volume = 206 | pages = 1–6 | date = July 2019 | pmid = 30898540 | doi = 10.1016/j.physbeh.2019.03.016 | s2cid = 81965422 }}</ref> In another study, serum 5-HT levels did not seem to be associated with dogs' behavioural response to a stressful situation.<ref>{{cite journal | vauthors = Riggio G, Mariti C, Sergi V, Diverio S, Gazzano A | title = Serotonin and Tryptophan Serum Concentrations in Shelter Dogs Showing Different Behavioural Responses to a Potentially Stressful Procedure | journal = Veterinary Sciences | volume = 8 | issue = 1 | pages = 1 | date = December 2020 | pmid = 33374183 | pmc = 7824451 | doi = 10.3390/vetsci8010001 | doi-access = free }}</ref> Urinary serotonin/creatinine ratio in bitches tended to be higher 4 weeks after surgery. In addition, serotonin was positively correlated with both cortisol and progesterone but not with testosterone after ovariohysterectomy.<ref>{{cite journal | vauthors = Hydbring-Sandberg E, Larsson E, Madej A, Höglund OV | title = Short-term effect of ovariohysterectomy on urine serotonin, cortisol, testosterone and progesterone in bitches | journal = BMC Research Notes | volume = 14 | issue = 1 | pages = 265 | date = July 2021 | pmid = 34246304 | pmc = 8272283 | doi = 10.1186/s13104-021-05680-y | doi-access = free }}</ref>

=====Teleost fish=====
Like non-placental vertebrates, teleost fish also possess 5-HT cells in other sections of the brain, including the [[basal forebrain]].<ref name="Backström_2017" /> ''[[Zebrafish|Danio rerio]]'' (zebra fish) are a species of teleost fish often used for studying serotonin within the brain. Despite much being unknown about serotonergic systems in vertebrates, the importance in moderating stress and social interaction is known.<ref name="Winberg_2016">{{cite journal | vauthors = Winberg S, Thörnqvist PO | title = Role of brain serotonin in modulating fish behavior | journal = Current Zoology | volume = 62 | issue = 3 | pages = 317–323 | date = June 2016 | pmid = 29491919 | pmc = 5804243 | doi = 10.1093/cz/zow037 }}</ref> It is hypothesized that AVT and CRF cooperate with serotonin in the [https://link.springer.com/referenceworkentry/10.1007%2F978-1-4419-1005-9_460 hypothalamic-pituitary-interrenal axis].<ref name="Backström_2017" /> These [[neuropeptide]]s influence the [[Neuroplasticity|plasticity]] of the teleost, affecting its ability to change and respond to its environment. Subordinate fish in social settings show a drastic increase in 5-HT concentrations.<ref name="Winberg_2016" /> High levels of 5-HT long term influence the inhibition of aggression in subordinate fish.<ref name="Winberg_2016" />

=====Mice=====
Researchers at the Department of Pharmacology and Medical Chemistry used serotonergic drugs on male mice to study the effects of selected drugs on their behavior.<ref name="Olivier_1989">{{cite journal | vauthors = Olivier B, Mos J, van der Heyden J, Hartog J | title = Serotonergic modulation of social interactions in isolated male mice | journal = Psychopharmacology | volume = 97 | issue = 2 | pages = 154–156 | date = 1989-02-01 | pmid = 2498921 | doi = 10.1007/BF00442239 | s2cid = 37170174 }}</ref> Mice in isolation exhibit increased levels of [[Agonistic behaviour|agonistic behavior]] towards one another. Results found that serotonergic drugs reduce aggression in isolated mice while simultaneously increasing social interaction.<ref name="Olivier_1989" /> Each of the treatments use a different mechanism for targeting aggression, but ultimately all have the same outcome. While the study shows that serotonergic drugs successfully target serotonin receptors, it does not show specifics of the mechanisms that affect behavior, as all types of drugs tended to reduce aggression in isolated male mice.<ref name="Olivier_1989" /> Aggressive mice kept out of isolation may respond differently to changes in serotonin reuptake.

====Behavior====
Like in humans, serotonin is extremely involved in regulating behavior in most other vertebrates. This includes not only response and social behaviors, but also influencing mood. Defects in serotonin pathways can lead to intense variations in mood, as well as symptoms of mood disorders, which can be present in more than just humans.

=====Social interaction=====
One of the most researched aspects of social interaction in which serotonin is involved is aggression. Aggression is regulated by the 5-HT system, as serotonin levels can both induce or inhibit aggressive behaviors, as seen in mice (see section on Mice) and crabs.<ref name="Olivier_1989" /> While this is widely accepted, it is unknown if serotonin interacts directly or indirectly with parts of the brain influencing aggression and other behaviors.<ref name="Bacqué-Cazenave_2020" /> Studies of serotonin levels show that they drastically increase and decrease during social interactions, and they generally correlate with inhibiting or inciting aggressive behavior.<ref>{{cite journal | vauthors = Huber R, Smith K, Delago A, Isaksson K, Kravitz EA | title = Serotonin and aggressive motivation in crustaceans: altering the decision to retreat | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 11 | pages = 5939–5942 | date = May 1997 | pmid = 9159179 | pmc = 20885 | doi = 10.1073/pnas.94.11.5939 | doi-access = free | bibcode = 1997PNAS...94.5939H }}</ref> The exact mechanism of serotonin influencing social behaviors is unknown, as pathways in the 5-HT system in various vertebrates can differ greatly.<ref name="Bacqué-Cazenave_2020" />

=====Response to stimuli=====
Serotonin is important in environmental response pathways, along with other [[neurotransmitter]]s.<ref>{{cite journal | vauthors = Sanchez CL, Biskup CS, Herpertz S, Gaber TJ, Kuhn CM, Hood SH, Zepf FD | title = The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications | journal = The International Journal of Neuropsychopharmacology | volume = 18 | issue = 10 | pages = pyv050 | date = May 2015 | pmid = 25991656 | pmc = 4648158 | doi = 10.1093/ijnp/pyv050 }}</ref> Specifically, it has been found to be involved in auditory processing in social settings, as primary sensory systems are connected to social interactions.<ref name="Petersen_2017">{{cite journal | vauthors = Petersen CL, Hurley LM | title = Putting it in Context: Linking Auditory Processing with Social Behavior Circuits in the Vertebrate Brain | journal = Integrative and Comparative Biology | volume = 57 | issue = 4 | pages = 865–877 | date = October 2017 | pmid = 28985384 | pmc = 6251620 | doi = 10.1093/icb/icx055 }}</ref> Serotonin is found in the [[Inferior colliculus|IC structure]] of the midbrain, which processes specie specific and non-specific social interactions and vocalizations.<ref name="Petersen_2017" /> It also receives acoustic projections that convey signals to auditory processing regions.<ref name="Petersen_2017" /> Research has proposed that serotonin shapes the auditory information being received by the IC and therefore is influential in the responses to auditory stimuli.<ref name="Petersen_2017" /> This can influence how an organism responds to the sounds of predatory or other impactful species in their environment, as serotonin uptake can influence aggression or social interaction.

=====Mood=====
We can describe mood not as specific to an emotional status, but as associated with a relatively long-lasting emotional state. Serotonin's association with mood is most known for various forms of depression and bipolar disorders in humans.<ref name="Lucki_1998" /> Disorders caused by serotonergic activity potentially contribute to the many symptoms of major depression, such as overall mood, activity, suicidal thoughts and sexual and [[cognitive dysfunction]]. [[Selective serotonin reuptake inhibitor]]s (SSRI's) are a class of drugs demonstrated to be an effective treatment in major depressive disorder and are the most prescribed class of antidepressants. SSRI's function is to block the reuptake of serotonin, making more serotonin available to absorb by the receiving neuron. Animals have been studied for decades in order to understand depressive behavior among species. One of the most familiar studies, the forced swimming test (FST), was performed to measure potential antidepressant activity.<ref name="Lucki_1998" /> Rats were placed in an inescapable container of water, at which point time spent immobile and number of active behaviors (such as splashing or climbing) were compared before and after a panel of anti-depressant drugs were administered. Antidepressants that selectively inhibit NE reuptake were shown to reduce immobility and selectively increase climbing without affecting swimming. However, results of the SSRI's also show reduced immobility but increased swimming without affecting climbing. This study demonstrated the importance of behavioral tests for antidepressants, as they can detect drugs with an effect on core behavior along with behavioral components of species.<ref name="Lucki_1998" />