FLUOKSETİNE BAĞLI KİLO DEĞİŞİMİNİN SEROTONİN 2C RESEPTÖRÜ İLE İLİŞKİSİNİN İNCELENMESİ

The serotonergic system links mood and energy balance through the serotonin 2C receptor (5-HT2CR) on hypothalamic proopiomelanocortin (POMC) neurons. Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI), is considered weight-neutral in the short term, but its chronic effects on this circuit are unclear. We hypothesized that chronic FLX alters hypothalamic neuropeptide levels via the 5-HT2CR, causing weight gain, and that the 5-HT2CR antagonist SB242084 reverses this, partly through mRNA editing. Male C57BL/6J mice received FLX, SB242084 or both for 60 days; body weight, novelty-suppressed feeding (NSFT) and forced swim (FST) behavior, hypothalamic Htr2c, Pomc and Npy expression, and 5-HT2CR editing were assessed. FLX increased weight gain alone and with SB242084; SB242084 alone had no effect. FLX prolonged NSFT arena latency, an anxiogenic effect reversed by SB242084, and halved FST mobility alone and in combination. All treatments reduced 5-HT2CR expression, most strongly in combination; FLX raised Npy without changing Pomc, whereas the combination raised Pomc. FLX also increased editing at Site A (I156V), which lowers receptor signaling efficiency. Chronic FLX therefore promotes weight gain and remodels the hypothalamic feeding circuit, a response modified but not prevented by 5-HT2CR blockade.