Reevaluation of anti-obesity action of mazindol and elucidation of its effect on the reward system. (28th October 2016)

• Record Type: Journal Article
• Authors: Aotani, Daisuke; Son, Cheol; Shimizu, Yoshiyuki; Nomura, Hidenari; Hikida, Takatoshi; Kusakabe, Toru; Tanaka, Tomohiro; Miyazawa, Takashi; Hosoda, Kiminori; Nakao, Kazuwa
• Is Part Of: Neuroscience letters. Volume 633(2016)
• Page Start: 141
• Page End: 145
• Publication Date: 2016-10-28
• Subjects: ANOVA analysis of variance -- AUC area under the curve -- CPP conditioned place preference -- DIO diet induced obesity -- HFD high fat diet -- NCD normal chow diet; Mazindol -- Obesity -- High fat diet -- Reward system -- Conditioned place preference; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.09.014
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Mazindol reduces body weight gain and hyperphagia induced by high-fat diet. Mazindol decreases preference for lipid emulsion. Mazindol decreases conditioned place preference for high-fat diet. Mazindol at the dose required for these effects does not elicit abuse potential. 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 (1.5 mg/kg/day) for 28 days. A single intraperitoneal administration of mazindol (1.5 mg/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 (1.5 mg/kg) significantly decreased CPP score for HFD as compared with vehicle (vehicle, 330.44 ± 58.61 s; mazindol, 144.72 ± 43.02 s; 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.