{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T09:08:19Z","timestamp":1719911299404},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,9,6]],"date-time":"2012-09-06T00:00:00Z","timestamp":1346889600000},"content-version":"vor","delay-in-days":341,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:p>Because the use of monoamine reuptake inhibitors as weight\u2010reducing agents is limited by adverse effects, novel antiobesity drugs are needed. We studied acute effects of the noradrenaline (NA) and serotonin (5\u2010HT) reuptake inhibitor sibutramine (SIB), alone and after pretreatment with \u03b11\u2010 and \u03b12\u2010adrenoceptor (AR), and 5\u2010HT1\/2\/7, 5\u2010HT1B and 5\u2010HT2C receptor antagonists in order to determine which ARs and 5\u2010HT receptors act downstream of SIB on feeding and locomotion. Acute effects on caloric and water intake, meal microstructure and locomotion were assessed, using an automated weighing system and telemetry in male rats with restricted 18\u2010h access to Western style diet. SIB 3 mg\/kg reduced meal size and frequency, which suggests enhanced within\u2010 and postmeal satiety. Imiloxan (\u03b12B\u2010AR), WB4101 (\u03b11\u2010AR), SB\u2010224289 (5\u2010HT1B), and modestly BRL 44408 (\u03b12A\/D\u2010AR) attenuated SIB's effect on meal size, suggesting that \u03b12B\u2010 and \u03b11\u2010ARs and 5\u2010HT1B receptors mediate within\u2010meal satiety, with a modest role for \u03b12A\/D\u2010ARs. Only prazosin (\u03b11\/2B\/2C\u2010AR) counteracted SIB's effect on meal frequency. At 3 mg\/kg, SIB modestly increased locomotion. This effect was blocked by metergoline (5\u2010HT1\/2\/7), WB4101 (\u03b11\u2010AR), and RX821002 (\u03b12\u2010AR). Interestingly, the \u03b12\u2010AR antagonists atipamezole and RX821002 enhanced SIB's effect on caloric intake, probably due to inverse agonistic actions at \u03b12A\u2010autoreceptors that further enhanced release of NA that regulates caloric intake. Thus, an inverse agonist of presynaptic \u03b12A\u2010ARs might beneficially enhance SIB's weight\u2010reducing effect and offer novel treatment for obesity. All in all, the present data supports the ARs and 5\u2010HT receptors involved in the effects of SIB on different aspects of caloric intake and locomotion.<\/jats:p>","DOI":"10.1038\/oby.2011.51","type":"journal-article","created":{"date-parts":[[2011,4,7]],"date-time":"2011-04-07T22:45:06Z","timestamp":1302216306000},"page":"1979-1986","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Inverse Agonism at \u03b12A Adrenoceptors Augments the Hypophagic Effect of Sibutramine in Rats"],"prefix":"10.1002","volume":"19","author":[{"given":"Sanna K.","family":"Janhunen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther M.","family":"van der Zwaal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne E.","family":"La 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