Decreased Intake of Sucrose Solutions in Orexin Knockout Mice Eiko Matsuo & Ayako Mochizuki & Kiyomi Nakayama & Shiro Nakamura & Takashi Yamamoto & Seiji Shioda & Takeshi Sakurai & Masashi Yanagisawa & Tetsuya Shiuchi & Yasuhiko Minokoshi & Tomio Inoue Received: 11 September 2010 / Accepted: 4 November 2010 # Springer Science+Business Media, LLC 2010 Abstract Orexins are synthesized by lateral hypothalamic neurons and are suggested to be implicated in feeding behavior. Recent studies have shown that intracerebroven- tricular administration of orexin-A increases intake of sweet- tasting solution. Effects of suppressing the orexin system on consumption of sweet-tasting solution and sensory process- ing with sweet taste inputs, however, have yet to be examined. We examined the effects of orexin deficiency on sucrose solution intake, locomotor activity, and preference for sweet solution using male orexin knockout (OxKO) and littermate wild-type (WT) mice. In the dark and over 24-h periods, OxKO mice showed significantly less sucrose intake and lower locomotor activity than WT mice without alteration in food intake whereas preferences for 100 mM sucrose were not different between the genotypes. Moreover, sucrose intake of OxKO mice was significantly less than sucrose intake of a subgroup of WT mice with similar locomotor activity compared to that of OxKO mice. These results suggest that factors other than the lower energy expenditure due to lower locomotor activity are likely responsible for the decreased sucrose intake of OxKO mice. Orexin deficiency may lower the satiety threshold resulting in reduced sucrose intake, without altering food intake. Keywords Orexin . Sucrose intake . Locomotor activity . Two-bottle preference test E. Matsuo and A. Mochizuki contributed equally to this work. E. Matsuo : A. Mochizuki : K. Nakayama : S. Nakamura : T. Inoue (*) Department of Oral Physiology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan e-mail: inouet@dent.showa-u.ac.jp T. Yamamoto Faculty of Health Science, Kio University, 4-2-2 Umami-naka, Koryo-cho, Kitakatsuragi-gun, Nara 635-0832, Japan S. Shioda Department of Anatomy, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan T. Sakurai Department of Molecular Neuroscience and Integrative Physiology, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan M. Yanagisawa Howard Hughes Medical Institute and Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9050, USA T. Sakurai : M. Yanagisawa ERATO Yanagisawa Orphan Receptor Project, Japan Science and Technology Corporation, Tokyo 135-0064, Japan T. Shiuchi : Y. Minokoshi Division of Endocrinology and Metabolism, Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan T. Shiuchi : Y. Minokoshi Department of Physiological Sciences, The Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa 240-0193, Japan J Mol Neurosci DOI 10.1007/s12031-010-9475-1