Role of neuropeptide Y and proopiomelanocortin in fluoxetine-induced anorexia.
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).
Myung
Chang-Seon
CS
Laboratory in Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea. cm8r@cnu.ac.kr
Kim
Bom-Taeck
BT
Choi
Si Ho
SH
Song
Gyu Yong
GY
Lee
Seok Yong
SY
Jahng
Jeong Won
JW
D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism*; D001069:Appetite Regulation / Q000187:drug effects*; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry / Q000378:metabolism*; D001345:Autoradiography; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005473:Fluoxetine; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000378:metabolism*; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017367:Selective Serotonin Reuptake Inhibitors
D005473:Fluoxetine; D009478:Neuropeptide Y; D011333:Pro-Opiomelanocortin; D012313:RNA; D012333:RNA, Messenger; D017367:Selective Serotonin Reuptake Inhibitors