Document Detail


Milnacipran, a serotonin and norepinephrine reuptake inhibitor, induces appetite-suppressing effects without inducing hypothalamic stress responses in mice.
MedLine Citation:
PMID:  17218444     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Milnacipran, a selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor, increases extracellular 5-HT and NA levels equally in the central nervous system. Here, we report that systemic administration of milnacipran (20-60 mg/kg) significantly suppressed food intake after fasting in C57BL6J mice. The appetite-suppressing effects of milnacipran were sustained for 5 h. Neither SB242084, a selective 5-HT2C receptor antagonist, nor SB224289, a selective 5-HT1B receptor antagonist, reversed the appetite-suppressing effects of milnacipran. Milnacipran suppressed food intake and body weight in wild-type mice and in A(y) mice, which have ectopic expression of the agouti protein. Moreover, milnacipran significantly increased hypothalamic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA levels, while having no effect on hypothalamic neuropeptide Y, ghrelin, corticotropin-releasing hormone (CRH), and suppressor of cytokine signaling-3 mRNA levels. Interestingly, milnacipran did not increase plasma corticosterone and blood glucose levels, whereas fenfluramine, which inhibits 5-HT reuptake and stimulates 5-HT release, significantly increased plasma corticosterone and blood glucose levels in association with increased hypothalamic CRH mRNA levels. The appetite-suppressing effects of milnacipran had no effects on food intake in food-restricted, wild-type mice and A(y) mice. On the other hand, fenfluramine suppressed food intake in food-restricted wild-type mice, but it had no effects in food-restricted A(y) mice. These results suggest that inhibition of 5-HT and NA reuptake induces appetite-suppressing effects independent of 5-HT2C and 5-HT1B receptors, and increases hypothalamic POMC and CART gene expression without increasing plasma corticosterone and blood glucose levels in mice.
Authors:
Katsunori Nonogaki; Kana Nozue; Tomifusa Kuboki; Yoshitomo Oka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-11
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  292     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-05-03     Completed Date:  2007-07-02     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1775-81     Citation Subset:  IM    
Affiliation:
Center of Excellence, Division of Molecular Metabolism and Diabetes, Tohoku Univ Graduate School of Medicine, 2-1 Seiryo-Machi, Sendai, Japan. knonogaki-tky@umin.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adrenergic Uptake Inhibitors / pharmacology*
Animals
Appetite / drug effects*,  physiology
Appetite Depressants / pharmacology*
Blood Glucose / drug effects
Corticosterone / blood
Cyclopropanes / pharmacology*
Dose-Response Relationship, Drug
Feeding Behavior / drug effects
Fenfluramine / pharmacology
Food Deprivation
Hypothalamus / drug effects*,  physiology
Mice
Serotonin Uptake Inhibitors / pharmacology*
Stress, Physiological*
Chemical
Reg. No./Substance:
0/Adrenergic Uptake Inhibitors; 0/Appetite Depressants; 0/Blood Glucose; 0/Cyclopropanes; 0/Serotonin Uptake Inhibitors; 458-24-2/Fenfluramine; 50-22-6/Corticosterone; 92623-85-3/milnacipran

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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