title: Changes in 5-HT4 receptor and 5-HT transporter binding in olfactory bulbectomized and glucocorticoid receptor heterozygous mice.
abstract: The 5-HT(4) receptor is a new potential target for antidepressant treatment and may be implicated in the pathogenesis of depression. This study investigated differences in 5-HT(4) receptor and 5-HT transporter (5-HTT) binding by quantitative autoradiography of [(3)H]SB207145 and (S)-[N-methyl-(3)H]citalopram in two murine models of depression-related states, olfactory bulbectomy and glucocorticoid receptor heterozygous (GR(+/-)) mice. The olfactory bulbectomy model is characterized by 5-HT system changes, while the GR(+/-) mice have a deficit in hypothalamic-pituitary-adrenal (HPA) system control. The olfactory bulbectomized mice displayed increased activity in the open field test, a characteristic depression-like feature of this model. After bulbectomy, 5-HT(4) receptor binding was increased in the ventral hippocampus (12%) but unchanged in the dorsal hippocampus, frontal and caudal caudate putamen. Among post hoc analyzed regions, there was a 14% decrease in 5-HT(4) receptor binding in the olfactory tubercles. The 5-HTT binding was unchanged in the hippocampus and caudate putamen of bulbectomized mice but post hoc analysis showed small decreases in lateral septum and lateral globus pallidus. In comparison, GR(+/-) mice had increased 5-HT(4) receptor (11%) binding in the caudal caudate putamen and decreased 5-HTT binding in the frontal caudate putamen but no changes in dorsal and ventral hippocampus. Post hoc analysis showed increased 5-HT(4) receptor binding in the olfactory tubercles of GR(+/-) mice. In conclusion, we have found brain regional changes in 5-HT(4) receptor and 5-HTT transporter binding in two murine models of depression-related states, characterized by 5-HT and HPA system changes.
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. cecilie@nru.dk
authors.forename: Cecilie L
authors.initials: CL
authors.lastname: Licht
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Kirkegaard
authors.forename: Maha
authors.initials: M
authors.lastname: Zueger
authors.forename: Sabine
authors.initials: S
authors.lastname: Chourbaji
authors.forename: Peter
authors.initials: P
authors.lastname: Gass
authors.forename: Susana
authors.initials: S
authors.lastname: Aznar
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology; D015283:Citalopram; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009830:Olfactory Bulb / Q000502:physiology*; D010880:Piperidines / Q000378:metabolism; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000502:physiology*; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors
chemical_list: D015283:Citalopram; D010880:Piperidines; D011965:Receptors, Glucocorticoid; D044422:Receptors, Serotonin, 5-HT4; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C534709:SB 207145