title: Possible involvement of serotonin 5-HT2 receptor in the regulation of feeding behavior through the histaminergic system.
abstract: The central histaminergic system has been proven to be involved in several physiological functions including feeding behavior. Some atypical antipsychotics like risperidone and aripiprazole are known to affect feeding behavior and to antagonize the serotonin (5-HT) receptor subtypes. To examine the possible neural relationship between the serotonergic and histaminergic systems in the anorectic effect of the antipsychotics, we studied the effect of a single administration of these drugs on food intake and hypothalamic histamine release in mice using in vivo microdialysis. Single injection of risperidone (0.5mg/kg, i.p.) or aripiprazole (1mg/kg, i.p.), which have binding affinities to 5-HT(1A, 2A, 2B) and (2C) receptors decreased food intake in C57BL/6N mice with concomitant increase of hypothalamic histamine release. However, a selective D(2)-antagonist, haloperidol (0.5mg/kg, i.p.), did not have effects on food intake or histamine release. Furthermore, in histamine H(1) receptor-deficient mice, there was no reduction of food intake induced by atypical antipsychotics, although histamine release was increased. Moreover, selective 5-HT(2A)-antagonists, volinanserin (0.5, 1mg/kg, i.p.) and ketanserin (5, 10mg/kg, i.p.), significantly increased histamine release and 5-HT(2B/2C) -antagonist, SB206553 (2.5, 5mg/kg, i.p.), slightly increased it. On the contrary, 5-HT(1A) -selective antagonist, WAY100635 (1, 2mg/kg), did not affect the histaminergic tone. These findings suggest that serotonin tonically inhibits histamine release via 5-HT(2) receptors and that antipsychotics enhance the release of hypothalamic histamine by blockade of 5-HT(2) receptors resulting in anorexia via the H(1) receptor.
authors.affiliation: Department of Medical Science and Technology, Division of Health Sciences, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan. murotani@med.kobe-u.ac.jp
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Murotani
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Yuka
authors.initials: Y
authors.lastname: Isogawa
authors.forename: Michitaka
authors.initials: M
authors.lastname: Karashima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamatodani
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011969:Receptors, Histamine H1 / Q000172:deficiency* / Q000235:genetics; D044348:Receptors, Serotonin, 5-HT2 / Q000502:physiology*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology
chemical_list: D011969:Receptors, Histamine H1; D044348:Receptors, Serotonin, 5-HT2; D058830:Serotonin 5-HT2 Receptor Antagonists; D006632:Histamine