Role of neuropeptide Y and proopiomelanocortin in fluoxetine-induced anorexia.

Laboratory in Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea.
Archives of Pharmacal Research (Impact Factor: 1.75). 07/2005; 28(6):716-21. DOI: 10.1007/BF02969363
Source: PubMed

ABSTRACT Fluoxetine is an anorexic agent known to reduce food intake and weight gain. However, the molecular mechanism by which fluoxetine induces anorexia has not been well-established. We examined mRNA expression levels of neuropeptide Y (NPY) and proopiomelanocortin (POMC) in the brain regions of rats using RT-PCR and in situ hybridization techniques after 2 weeks of administering fluoxetine daily. Fluoxetine persistently suppressed food intake and weight gain during the experimental period. The pair-fed group confirmed that the reduction in body weight in the fluoxetine treated rats resulted primarily from decreased food intake. RT-PCR analyses showed that mRNA expression levels of both NPY and POMC were markedly reduced by fluoxetine treatment in all parts of the brain examined, including the hypothalamus. POMC mRNA in situ signals were significantly decreased, NPY levels tended to increase in the arcuate nucleus (ARC) of fluoxetine treated rats (compared to the vehicle controls). In the pair-fed group, NPY mRNA levels did not change, but the POMC levels decreased (compared with the vehicle controls). These results reveal that the chronic administration of fluoxetine decreases expression levels in both NPY and POMC in the brain, and suggests that fluoxetine-induced anorexia may not be mediated by changes in the ARC expression of either NPY or POMC. It is possible that a fluoxetine raised level of 5-HT play an inhibitory role in the orectic action caused by a reduced expression of ARC POMC (alpha-MSH).

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    • "Rats in each cage were assigned together either for fluoxetine or for vehicle, randomly. The chronic dosage of fluoxetine used in this study significantly suppressed food intake in adult rats (Myung et al., 2005), and was proved to maintain the serum fluoxetine levels corresponding to an effective therapeutic dose for depressed patients (Dulawa et al., 2004). "
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    • "However, 5-HTP injections did not increase the expression of proopiomelanocortin (POMC), functional precursor of α-MSH, in the arcuate nucleus (our unpublished observation). We have previously reported that the arcuate POMC expression is decreased by chronic treatment with selective 5-HT reuptake inhibitor fluoxetine known to increase the brain 5-HT level (Myung et al., 2005). Thus, it is concluded that the increased pERK1/2 in the PVN of 5-HTP injected rats is less likely due to an activation of melanocortin pathways. "
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