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Figure 4. Rats were treated (po), with vehicle (0 mgkgÀ1) or ACT-335827 (300 mgkgÀ1) or fluoxetine (30 mgkgÀ1), 1 h before testing in the schedule-induced
polydipsia paradigm. The average fluid intake (panels a and b) and the number of head entries (panels c and d) into the food dispenser were monitored
during the 2 h test session. Control home cage water intake with ACT-335827 was assessed over the 12 h dark period (panel e). Data shown are the mean
ÆSEM of n=11–15 animals in a within-subjects cross-over design; * <0.05 vs. control (0 mgkgÀ1).
Figure 5. Telemetrized rats were treated (po) with vehicle or ACT-335827 (300 mgkgÀ1) at the end of the light phase, and the time spent in a) active wake,
b) quiet wake, c) non-REM sleep, and d) REM sleep was assessed during the following 12 h. Data shown are the mean ÆSEM of n=8 animals in a within-sub-
jects cross-over design. ACT-335827 had no significant effect on the duration of wake and sleep stages.
the dual OXR antagonist almorexant. However, in contrast to
Keywords: anxiety
· neurotransmitters · orexin receptor
almorexant, ACT-335827 did not decrease wakefulness. ACT-
335827 may serve as a novel pharmacological tool to further
explore the specific role of OXR-1 signaling in physiology and
behavior.
antagonists · peptides · sleep
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Experimental Section
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Acknowledgements
For expert technical and conceptual support, the authors thank
Ursula Fusco-Hug, Pascal Rebmann, Stephane Delahaye, Stepha-
nie Hertzog, Julia Friedrich, Isabelle Weber, Cedric Fischer, Malvi-
na Louis, Helene Roellinger, Hugues Lecourt, Carla Sciarretta, Re-
bekka Pietrek, Monica Gaiffi, Thomas Sasse, Celia Mꢀller-Grand-
jean, Katalin Menyhart, Markus von Raumer, Bruno Capeleto, and
Roberto Bravo (all employees of Actelion Pharmaceuticals Ltd,
Allschwil, Switzerland).
[12] C. D. Cox, M. J. Breslin, D. B. Whitman, J. D. Schreier, G. B. McGaughey,
M. J. Bogusky, A. J. Roecker, S. P. Mercer, R. A. Bednar, W. Lemaire, J. G.
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemMedChem 2013, 8, 898 – 903 902