Editing Dopamine (section)

===Psychosis and antipsychotic drugs===
{{Main|Psychosis}}
Psychiatrists in the early 1950s discovered that a class of drugs known as [[typical antipsychotic]]s (also known as major [[tranquilizer]]s), were often effective at reducing the [[psychotic]] symptoms of schizophrenia.<ref name=Healy/> The introduction of the first widely used antipsychotic, [[chlorpromazine]] (Thorazine), in the 1950s, led to the release of many patients with schizophrenia from institutions in the years that followed.<ref name=Healy/> By the 1970s researchers understood that these typical antipsychotics worked as [[receptor antagonists|antagonists]] on the D<sub>2</sub> receptors.<ref name=Healy/><ref name=Brunton>{{cite book | vauthors = Brunton L | title = Goodman and Gilman's The Pharmacological Basis of Therapeutics|publisher=McGraw Hill|pages=417–55|edition=12th}}</ref> This realization led to the so-called [[dopamine hypothesis of schizophrenia]], which postulates that schizophrenia is largely caused by hyperactivity of brain dopamine systems.<ref name="Howes">{{cite journal | vauthors = Howes OD, Kapur S | title = The dopamine hypothesis of schizophrenia: version III—the final common pathway | journal = Schizophrenia Bulletin | volume = 35 | issue = 3 | pages = 549–62 | date = May 2009 | pmid = 19325164 | pmc = 2669582 | doi = 10.1093/schbul/sbp006 }}</ref> The dopamine hypothesis drew additional support from the observation that psychotic symptoms were often intensified by dopamine-enhancing stimulants such as methamphetamine, and that these drugs could also produce psychosis in healthy people if taken in large enough doses.<ref name=Howes/> In the following decades other [[atypical antipsychotics]] that had fewer serious side effects were developed.<ref name=Healy/> Many of these newer drugs do not act directly on dopamine receptors, but instead produce alterations in dopamine activity indirectly.<ref name=Horacek>{{cite journal | vauthors = Horacek J, Bubenikova-Valesova V, Kopecek M, Palenicek T, Dockery C, Mohr P, Höschl C | s2cid = 18226404 | title = Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia | journal = CNS Drugs | volume = 20 | issue = 5 | pages = 389–409 | year = 2006 | pmid = 16696579 | doi = 10.2165/00023210-200620050-00004 }}</ref> These drugs were also used to treat other psychoses.<ref name=Healy>{{Cite book |title=The Creation of Psychopharmacology | vauthors = Healy D |year=2004 |publisher=Harvard University Press |pages=37–73  |isbn=978-0-674-01599-9 }}</ref> [[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.<ref name=Brunton/>

Later observations, however, have caused the dopamine hypothesis to lose popularity, at least in its simple original form.<ref name=Howes/> For one thing, patients with schizophrenia do not typically show measurably increased levels of brain dopamine activity.<ref name=Howes/> Even so, many psychiatrists and neuroscientists continue to believe that schizophrenia involves some sort of dopamine system dysfunction.<ref name=Healy/> As the "dopamine hypothesis" has evolved over time, however, the sorts of dysfunctions it postulates have tended to become increasingly subtle and complex.<ref name=Healy/>

[[Psychopharmacology|Psychopharmacologist]] [[Stephen Stahl|Stephen M. Stahl]] suggested in a review of 2018 that in many cases of psychosis, including schizophrenia, three interconnected networks based on dopamine, serotonin, and glutamate – each on its own or in various combinations – contributed to an overexcitation of dopamine D<sub>2</sub> receptors in the [[ventral striatum]].<ref name="pmid29954475">{{cite journal| vauthors = Stahl SM| title=Beyond the dopamine hypothesis of schizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate. | journal=CNS Spectr | year= 2018 | volume= 23 | issue= 3 | pages= 187–91 | pmid=29954475 | doi=10.1017/S1092852918001013 | s2cid=49599226 | url=https://www.cambridge.org/core/services/aop-cambridge-core/content/view/3E9E50ED717219011DD1B570365010E8/S1092852918001013a.pdf/beyond_the_dopamine_hypothesis_of_schizophrenia_to_three_neural_networks_of_psychosis_dopamine_serotonin_and_glutamate.pdf |archive-url=https://web.archive.org/web/20200429212444/https://www.cambridge.org/core/services/aop-cambridge-core/content/view/3E9E50ED717219011DD1B570365010E8/S1092852918001013a.pdf/beyond_the_dopamine_hypothesis_of_schizophrenia_to_three_neural_networks_of_psychosis_dopamine_serotonin_and_glutamate.pdf |archive-date=2020-04-29 |url-status=live }}</ref>