{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:47:06Z","timestamp":1791179226265,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3408,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,10]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The effects of sibutramine (0.25\u201310\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> i.p.) on extracellular noradrenaline concentration in the frontal cortex and hypothalamus of freely\u2010moving rats were investigated using microdialysis. The role of presynaptic \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors in modulating the effects of sibutramine in these brain areas was also determined.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sibutramine induced an increase in extracellular noradrenaline concentration, the magnitude of which paralleled dose, in both brain areas. In the cortex, this increase was gradual and sustained, whereas in the hypothalamus it was more rapid and of shorter duration.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In both the cortex and hypothalamus, pretreatment of rats with the \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor antagonist RX821002 (3\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> i.p.) potentiated increases in the accumulation of extracellular noradrenaline induced by sibutramine (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> i.p.), by 7 and 10 fold respectively. RX821002 also reduced the latency of sibutramine to reach its maximum effect in the cortex, but not in the hypothalamus.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Infusion of RX821002 (1\u2003\u03bc<jats:sc>M<\/jats:sc>) <jats:italic>via<\/jats:italic> the probe increased the accumulation of extracellular noradrenaline induced by sibutramine (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> i.p.) in both brain areas. In the hypothalamus, the effects of RX821002 on the accumulation of noradrenaline induced by sibutramine were 2 fold greater than those in the cortex.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These findings support evidence that sibutramine inhibits the reuptake of noradrenaline <jats:italic>in vivo<\/jats:italic>, but that the accumulation of extracellular noradrenaline is limited by noradrenergic activation of presynaptic \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors. Furthermore, the data suggest that terminal \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors in the hypothalamus exert a greater inhibitory effect over the control of extracellular noradrenaline accumulation than do those in the cortex.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p> <jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>128<\/jats:bold>, 659\u2013666; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702859\">10.1038\/sj.bjp.0702859<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702859","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:12:18Z","timestamp":1106943138000},"page":"659-666","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Modulation of sibutramine\u2010induced increases in extracellular noradrenaline concentration in rat frontal cortex and hypothalamus by \u03b1<sub>2<\/sub>\u2010adrenoceptors"],"prefix":"10.1111","volume":"128","author":[{"given":"K E","family":"Wortley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D J","family":"Heal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S C","family":"Stanford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(76)90297-3"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(95)00134-4"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(93)90181-2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb14962.x"},{"key":"e_1_2_6_6_1","first-page":"642","article-title":"Presynaptic \u03b12\u2010adrenoceptors play a major role in the effects of idazoxan on cortical noradrenaline (as measured by in vivo dialysis) in the rat","volume":"241","author":"DENNIS T.","year":"1987","journal-title":"J. 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