title: Reevaluation of anti-obesity action of mazindol and elucidation of its effect on the reward system.
abstract: In this study, we evaluated the preventive effect of mazindol on the development of obesity and sought to elucidate the drug's effects on the reward system. In mice, body weight gain and hyperphagia induced by high-fat diet (HFD) were decreased by 38.6% and 13.9%, respectively, by subcutaneous infusion of mazindol (1.5mg/kg/day) for 28days. A single intraperitoneal administration of mazindol (1.5mg/kg) significantly reduced lipid preference, as assessed using the two-bottle preference paradigm (vehicle, 89.98±1.66%; mazindol, 75.65±5.47%; p<0.05). In addition, the conditioned place preference (CPP) test demonstrated that mazindol (1.5mg/kg) significantly decreased CPP score for HFD as compared with vehicle (vehicle, 330.44±58.61s; mazindol, 144.72±43.02s; p<0.05). Moreover, at the dose required for these effects, mazindol did not elicit abuse potential or induce psychostimulant-like behavior. These results confirm that mazindol prevents diet-induced obesity without addictive behavior and demonstrate that its action is mediated at least in part via the reward system, advancing our understanding of mazindol in clinical practice.
authors.affiliation: Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: aotani@kuhp.kyoto-u.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aotani
authors.affiliation: Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Cheol
authors.initials: C
authors.lastname: Son
authors.affiliation: Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hidenari
authors.initials: H
authors.lastname: Nomura
authors.affiliation: Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Hikida
authors.affiliation: Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kusakabe
authors.affiliation: Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyazawa
authors.affiliation: Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.affiliation: Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: nakao@kuhp.kyoto-u.ac.jp.
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage; D004361:Drug Tolerance; D005518:Food Preferences / Q000187:drug effects; D055104:Infusions, Subcutaneous; D008297:Male; D008454:Mazindol / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D012201:Reward
chemical_list: D019440:Anti-Obesity Agents; D004041:Dietary Fats; D008454:Mazindol
keywords: Conditioned place preference; High fat diet; Mazindol; Obesity; Reward system