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14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de
Major depression is one of the most common mental disorders worldwide, with serious social and economic consequences. There are many different hypotheses concerning the pathophysiology of this disease. The complex brain serotonin system and particularly the serotonin1A receptors (5-HT1AR) apparently play a pivotal role in the development of depression. The involvement of an altered, 5-HT1AR-mediated signalling in adult neurogenesis is also discussed. However, in this context the effects of pre- and postsynaptically located 5-HT1ARs have not been clarified yet. Mice with a permanent overexpression of postsynaptic 5-HT1ARs (OE mice) represent a unique tool to elucidate the effects of postsynaptic 5-HT1ARs in adult neurogenesis and depressive-like behaviour. Previous studies demonstrated an increased proliferation and survival of newborn cells in the adult dentate gyrus of female OE mice in comparison to controls. In the present study, we investigate the proliferation and survival of adult born cells after chronic treatment (15 days) with the selective 5-HT1AR agonist 8-OH-DPAT (0,5 mg/kg/day) in young adult OE and WT mice. On the last three days of treatment, newly generated cells of OE and WT mice are labelled by injections with bromodeoxyuridine (BrdU; 50 mg/kg/day). Mice are sacrificed either one day (proliferation) or 21 days (survival) after the last injection. We hypothesise that the data we will present will confirm our previous results, with possibly more pronounced proneurogenic effects and differences in male mice. Further immunohistochemical studies post-exercise and behavioural analyses are in progress to identify the relation between chronic postsynaptic 5-HT1AR stimulation, depressive-like behaviour and hippocampusdependent learning.