Unaltered Instrumental Learning and Attenuated Body-Weight Gain in Rats During Non-rotating Simulated Shiftwork C. H. C. Leenaars, 1 A. Kalsbeek, 2,3 M. A. J. Hanegraaf, 1 E. Foppen, 2,3 R. N. J. M. A. Joosten, 1 G. Post, 1 M. Dematteis, 4,5,6 M. G. P. Feenstra, 1,7,8 and E. J. W. van Someren 1,9 1 Department of Sleep and Cognition, Netherlands Institute for Neuroscience (NIN), The Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands, 2 Department of Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience (NIN), The Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands, 3 Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 4 Université Joseph Fourier, Grenoble 1, Faculté de Médecine, Grenoble, France, 5 INSERM U1042, Grenoble, France, 6 CHU Hôpital A. Michallon, Pôle Pluridisciplinaire de Médecine, Grenoble, France, 7 Department of Neuromodulation of Behaviour, Netherlands Institute for Neuroscience (NIN), The Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands, 8 Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 9 Department of Integrative Neurophysiology, Faculty of Earth and Life Sciences, VU University De Boelelaan, Amsterdam, The Netherlands Exposure to shiftwork has been associated with multiple health disorders and cognitive impairments in humans. We tested if we could replicate metabolic and cognitive consequences of shiftwork, as reported in humans, in a rat model comparable to 5 wks of non-rotating night shifts. The following hypotheses were addressed: (i) shiftwork enhances body-weight gain, which would indicate metabolic effects; and (ii) shiftwork negatively affects learning of a simple goal-directed behavior, i.e., the association of lever pressing with food reward (instrumental learning), which would indicate cognitive effects. We used a novel method of forced locomotion to model work during the animals’ normal resting period. We first show that Wistar rats, indeed, are active throughout a shiftwork protocol. In contrast with previous findings, the shiftwork protocol attenuated the normal weight gain to 76 ± 8 g in 5 wks as compared to 123 ± 15 g in the control group. The discrepancy with previous work may be explained by the concurrent observation that with our shiftwork protocol rats did not adjust their between-work circadian activity pattern. They maintained a normal level of activity during the “off-work” periods. In the control experiment, rats were kept active during the dark period, normally dominated by activity. This demonstrated that forced activity, per se, did not affect body-weight gain (mean±SEM: 85 ± 11 g over 5 wks as compared to 84 ± 11 g in the control group). Rats were trained on an instrumental learning paradigm during the fifth week of the protocol. All groups showed equivalent increases in lever pressing from the first (3.8 ± .7) to the sixth (21.3 ± 2.4) session, and needed a similar amount of sessions (5.1 ± .3) to reach a learning criterion (≥27 out of 30 lever presses). These results suggest that while on prolonged non-rotating shiftwork, not fully reversing the circadian rhythm might actually be beneficial to prevent body-weight gain and cognitive impairments. (Author correspondence: C.Leenaars@nin.knaw.nl) Keywords: Activity, Body-weight gain, Circadian phase, Cognition, Instrumental learning, Night shift, Shiftwork, Sleep INTRODUCTION Exposure to shiftwork has been associated with health problems, including cardiovascular, gastrointestinal, psy- chiatric, and neurological disorders (Driesen et al., 2010; Wong et al., 2010). Desynchronization of the circadian system by shiftwork and sleep deprivation may contrib- ute to the development of obesity (Chen, et al., 2010; Ekmekcioglu & Touitou, 2011; Spiegel et al., 2009; Tanaka et al., 2010). Multiple studies report an elevated body mass index (BMI; a measure for body weight rela- tive to height) in shiftworkers as compared to daytime workers (Croce et al., 2007; Kroenke et al., 2007; Morika- wa et al., 2007; Parkes, 2002). In a sample of Italian rail- road workers, shiftworkers had a higher BMI compared to daytime workers, even though the quality of their diet was better (Croce et al., 2007). Furthermore, Address correspondence to C. H. C. Leenaars, Department of Sleep and Cognition, Netherlands Institute for Neuroscience (NIN), The Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands. Tel: +31-20-5665495; Fax: +31-20- 5666121; Email: C.Leenaars@nin.knaw.nl Submitted October 8, 2011, Returned for revision November 18, 2011, Accepted December 26, 2011 Chronobiology International, 29(3): 344–355, (2012) Copyright © Informa Healthcare USA, Inc. ISSN 0742-0528 print/1525-6073 online DOI: 10.3109/07420528.2011.654018  Chronobiol Int Downloaded from informahealthcare.com by GlaxoSmithKline on 03/06/12 For personal use only.