{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T23:10:03Z","timestamp":1736723403255,"version":"3.32.0"},"reference-count":29,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:p>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\u201360 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<jats:sup>y<\/jats:sup>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<jats:sup>y<\/jats:sup>mice. On the other hand, fenfluramine suppressed food intake in food-restricted wild-type mice, but it had no effects in food-restricted A<jats:sup>y<\/jats:sup>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.<\/jats:p>","DOI":"10.1152\/ajpregu.00527.2006","type":"journal-article","created":{"date-parts":[[2007,1,12]],"date-time":"2007-01-12T01:35:01Z","timestamp":1168565701000},"page":"R1775-R1781","source":"Crossref","is-referenced-by-count":8,"title":["Milnacipran, a serotonin and norepinephrine reuptake inhibitor, induces appetite-suppressing effects without inducing hypothalamic stress responses in mice"],"prefix":"10.1152","volume":"292","author":[{"given":"Katsunori","family":"Nonogaki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kana","family":"Nozue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomifusa","family":"Kuboki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitomo","family":"Oka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1358\/dot.1998.34.8.485269"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01977-0"},{"key":"R3","unstructured":"Chaouloff F, Gunn SH, Young JB.Central 5-hydroxytryptamine2 receptors are involved in the adrenal catecholamine-releasing and hyperglycemic effects of the 5-hydroxytryptamine indirect agonistd-fenfluramine in the conscious rat.J Pharmacol Exp Ther260: 1008\u20131016, 1992."},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0173(93)90005-K"},{"key":"R5","doi-asserted-by":"crossref","unstructured":"Ebihara K, Ogawa Y, Katsuura G, Numata Y, Masuzaki H, Satoh N, Tamaki M, Yoshioka T, Hayase M, Matsuoka N, Aizawa-Abe M, Yoshimasa Y, Nakao K.Involvement of agouti-related protein. 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