Changes in 5-HT4 receptor and 5-HT transporter binding in olfactory bulbectomized and glucocorticoid receptor heterozygous mice

• Published in: Neurochemistry international 2010-03, Vol.56 (4), p.603-610
• Main Authors: LICHT, Cecilie L, KIRKEGAARD, Lisbeth, ZUEGER, Maha, CHOURBAJI, Sabine, GASS, Peter, AZNAR, Susana, KNUDSEN, Gitte M
• Format: Article
• Language: English
• Subjects: Animals; Autoradiography; Biological and medical sciences; Brain Chemistry - genetics; Brain Chemistry - physiology; Citalopram; Fundamental and applied biological sciences. Psychology; Image Processing, Computer-Assisted; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity - physiology; Olfactory Bulb - physiology; Piperidines - metabolism; Protein Binding; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - physiology; Receptors, Serotonin, 5-HT4 - metabolism; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin Uptake Inhibitors; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2010.01.003

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.