title: Chronic fluvoxamine treatment changes 5-HT(2A/2C) receptor-mediated behavior in olfactory bulbectomized mice.
abstract: OBJECTIVE
  Olfactory bulbectomy (OBX) in rodents represents a valuable experimental model of depression. This study was designed to shed further light on the impact of putative serotonergic neuronal degeneration in OBX mice and to assess the effect of a widely used antidepressant on serotonergic related behavioral changes induced by OBX.
  
  
  METHODS
  Adult male ddY mice were subject to bilateral OBX or sham surgery. The serotonin (5-HT)(2A/2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) enhanced a head-twitch response (HTR) in OBX mice. Effects of 5-HT(2A), 5-HT(2C) antagonists and fluvoxamine were observed in OBX mice following DOI administration.
  
  
  RESULTS
  The HTR elicited by the administration of DOI (0.5 mg/kg and 1 mg/kg, i.p.) was increased about twofold in OBX mice when compared with controls on the 14th day after the surgery. The injection of ketanserin (0.025 mg/kg, i.p.), a 5-HT(2A) receptor antagonist, inhibited the enhancement of the DOI-induced HTR after OBX. Likewise, the administration of SB 242084 (1 mg/kg, s.c.), a 5-HT(2C) receptor antagonist, also inhibited the DOI-induced HTR in OBX mice. Chronic but not acute treatment with the antidepressant fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), suppressed the enhancement of DOI-induced HTR after OBX.
  
  
  CONCLUSIONS
  These findings indicate that OBX, and the subsequent degeneration of neurons projecting from the olfactory bulb, caused a supersensitivity of 5-HT(2A/2C) receptors which may be involved in symptoms of depression.
authors.affiliation: Department of Pharmacology, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Oba
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagawasai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onogi
authors.forename: Wataru
authors.initials: W
authors.lastname: Nemoto
authors.forename: Fukie
authors.initials: F
authors.lastname: Yaoita
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Arai
authors.forename: Koichi
authors.initials: K
authors.lastname: Tan-No
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tadano
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003866:Depressive Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D016666:Fluvoxamine / Q000494:pharmacology / Q000627:therapeutic use*; D019416:Head Movements / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009830:Olfactory Bulb / Q000601:surgery*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000662:Amphetamines; D016666:Fluvoxamine; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine