{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:53:42Z","timestamp":1791161622005,"version":"4.1.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"41","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,10,9]]},"abstract":"<jats:p>\n                    Anorexia nervosa is a growing concern in mental health, often inducing death. The potential neuronal deficits that may underlie abnormal inhibitions of food intake, however, remain largely unexplored. We hypothesized that anorexia may involve altered signaling events within the nucleus accumbens (NAc), a brain structure involved in reward. We show here that direct stimulation of serotonin (5-hydroxytryptamine, 5-HT) 4 receptors (5-HT\n                    <jats:sub>4<\/jats:sub>\n                    R) in the NAc reduces the physiological drive to eat and increases CART (cocaine- and amphetamine-regulated transcript) mRNA levels in fed and food-deprived mice. It further shows that injecting 5-HT\n                    <jats:sub>4<\/jats:sub>\n                    R antagonist or siRNA-mediated 5-HT\n                    <jats:sub>4<\/jats:sub>\n                    R knockdown into the NAc induced hyperphagia only in fed mice. This hyperphagia was not associated with changes in CART mRNA expression in the NAc in fed and food-deprived mice. Results include that 5-HT\n                    <jats:sub>4<\/jats:sub>\n                    R control CART mRNA expression into the NAc via a cAMP\/PKA signaling pathway. Considering that CART may interfere with food- and drug-related rewards, we tested whether the appetite suppressant properties of 3,4-\n                    <jats:italic>N<\/jats:italic>\n                    -methylenedioxymethamphetamine (MDMA, ecstasy) involve the 5-HT\n                    <jats:sub>4<\/jats:sub>\n                    R. Using 5-HT\n                    <jats:sub>4<\/jats:sub>\n                    R knockout mice, we demonstrate that 5-HT\n                    <jats:sub>4<\/jats:sub>\n                    R are required for the anorectic effect of MDMA as well as for the MDMA-induced enhancement of CART mRNA expression in the NAc. Directly injecting CART peptide or CART siRNA into the NAc reduces or increases food consumption, respectively. Finally, stimulating 5-HT\n                    <jats:sub>4<\/jats:sub>\n                    R- and MDMA-induced anorexia were both reduced by injecting CART siRNA into the NAc. Collectively, these results demonstrate that 5-HT\n                    <jats:sub>4<\/jats:sub>\n                    R-mediated up-regulation of CART in the NAc triggers the appetite-suppressant effects of ecstasy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0701471104","type":"journal-article","created":{"date-parts":[[2007,10,3]],"date-time":"2007-10-03T20:53:32Z","timestamp":1191444812000},"page":"16335-16340","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":175,"title":["Anorexia induced by activation of serotonin 5-HT\n                    <sub>4<\/sub>\n                    receptors is mediated by increases in CART in the nucleus accumbens"],"prefix":"10.1073","volume":"104","author":[{"given":"Alexandra","family":"Jean","sequence":"first","affiliation":[{"name":"*Centre National de la Recherche Scientifique (CNRS), Unit\u00e9 Mixte de Recherche (UMR)5203, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U661, Universit\u00e9 Montpellier I and II, Institut de G\u00e9nomique Fonctionnelle, D\u00e9partement de Neurobiologie, 141 Rue de la Cardonille, F-34094 Montpellier Cedex 5, France;"},{"name":"Universit\u00e9 N\u00eemes (JE2425, Team 1, Anorexie, D\u00e9pendance, Ob\u00e9sit\u00e9 de N\u00eemes: ADON\u00eemes), Rue Docteur Georges Salan, F-30021 N\u00eemes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9gory","family":"Conductier","sequence":"additional","affiliation":[{"name":"*Centre National de la Recherche Scientifique (CNRS), Unit\u00e9 Mixte de Recherche (UMR)5203, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U661, Universit\u00e9 Montpellier I and II, Institut de G\u00e9nomique Fonctionnelle, D\u00e9partement de Neurobiologie, 141 Rue de la Cardonille, F-34094 Montpellier Cedex 5, France;"},{"name":"Universit\u00e9 N\u00eemes (JE2425, Team 1, Anorexie, D\u00e9pendance, Ob\u00e9sit\u00e9 de N\u00eemes: ADON\u00eemes), Rue Docteur Georges Salan, F-30021 N\u00eemes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Manrique","sequence":"additional","affiliation":[{"name":"CNRS, UMR6149, Universit\u00e9 Aix-Marseille I, Neurobiologie Int\u00e9grative et Adaptative, 3 Place Victor Hugo, F-13331 Marseille Cedex 3, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Bouras","sequence":"additional","affiliation":[{"name":"H\u00f4pitaux Universitaires de Gen\u00e8ve, Division de Neuropsychiatrie, CH-1225 Ch\u00eane-bourg, Switzerland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Berta","sequence":"additional","affiliation":[{"name":"Universit\u00e9 N\u00eemes (JE2425, Team 1, Anorexie, D\u00e9pendance, Ob\u00e9sit\u00e9 de N\u00eemes: ADON\u00eemes), Rue Docteur Georges Salan, F-30021 N\u00eemes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Hen","sequence":"additional","affiliation":[{"name":"Center of Neurobiology and Behavior, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Charnay","sequence":"additional","affiliation":[{"name":"H\u00f4pitaux Universitaires de Gen\u00e8ve, Division de Neuropsychiatrie, CH-1225 Ch\u00eane-bourg, Switzerland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00ebl","family":"Bockaert","sequence":"additional","affiliation":[{"name":"*Centre National de la Recherche Scientifique (CNRS), Unit\u00e9 Mixte de Recherche (UMR)5203, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U661, Universit\u00e9 Montpellier I and II, Institut de G\u00e9nomique Fonctionnelle, D\u00e9partement de Neurobiologie, 141 Rue de la Cardonille, F-34094 Montpellier Cedex 5, 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