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BEHAVIORAL PHARMACOLOGY

Circadian-Dependent Learning and Memory Enhancement in Nociceptin Receptor-Deficient Mice with a Novel KUROBOX Apparatus Using Stress-Free Positive Cue Task

Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan (J.N., H.U.); Department of Anatomy, Nagasaki University School of Medicine, Nagasaki, Japan (M.K.); Department of Biological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto, Japan (H.T.); and Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherché Scientifique/Institut National de la Santé et de la RecherchéMédicale/Universite Louis Pasteur, Illkirch, France (B.L.K.)

Using the novel apparatus KUROBOX, learning and memory behaviors, as well as various parameters of movement activity, were reevaluated in mice deficient for nociceptin/orphanin FQ receptor (NOP^–/– mice) or µ-opioid receptor (MOP^–/– mice). This method has the advantages that no handling procedures are required throughout the experiments performed over 3 days, positive cue paradigms are used without water or shock stress, and the method does not disturb the nocturnal habit of mice. NOP^–/– mice displayed a significant enhancement of learning and memory under stress-free conditions, but there were no changes in the various physical and psychological parameters of movement activity (nest stay ratio, distance moved, speed and angle in the movement) and biological rhythm that were measured. Enhancement of nocturnal learning was observed during the first 12-h dark cycle, and enhancement of memory was observed at the beginning of the second dark cycle in NOP^–/– mice. In contrast, MOP^–/– mice showed no significant change in learning and memory behaviors or in physical and psychological parameters of movement activity, except for speed, MOP^–/– mice showed a significant decrease in speed of movement. Thus, the KUROBOX apparatus provides a useful alternative method to evaluate learning and memory activity under the more physiological conditions. In addition, this apparatus has an advantage that various physical and psychological parameters of movement activity affecting learning and memory behavior are also evaluated at the same time.

Address correspondence to: Dr. Hiroshi Ueda, Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. E-mail: ueda{at}nagasaki-u.ac.jp