Mice Genetically Deficient in Vasopressin V1a and V1b Receptors Are Resistant to Jet Lag

Science 4 October 2013:
Vol. 342 no. 6154 pp. 85-90
DOI: 10.1126/science.1238599

Received for publication 1 April 2013

Yoshiaki Yamaguchi [1], Toru Suzuki [1], Yasutaka Mizoro [1], Hiroshi Kori [2,3], Kazuki Okada [1], Yulin Chen [1], Jean-Michel Fustin [1], Fumiyoshi Yamazaki [1], Naoki Mizuguchi [1], Jing Zhang [4], Xin Dong [4], Gozoh Tsujimoto [5], Yasushi Okuno [6], Masao Doi [1], Hitoshi Okamura [1,4]

[1] Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
[2] Department of Information Sciences, Ochanomizu University, Tokyo 112-8620, Japan.
[3] CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
[4] Division of Molecular Brain Science, Department of Brain Science, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan.
[5] Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
[6] Department of Systems Biosciences for Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.

Jet-lag symptoms arise from temporal misalignment between the internal circadian clock and external solar time. We found that circadian rhythms of behavior (locomotor activity), clock gene expression, and body temperature immediately reentrained to phase-shifted light-dark cycles in mice lacking vasopressin receptors V1a and V1b (V1a–/–V1b–/–). Nevertheless, the behavior of V1a–/–V1b–/– mice was still coupled to the internal clock, which oscillated normally under standard conditions. Experiments with suprachiasmatic nucleus (SCN) slices in culture suggested that interneuronal communication mediated by V1a and V1b confers on the SCN an intrinsic resistance to external perturbation. Pharmacological blockade of V1a and V1b in the SCN of wild-type mice resulted in accelerated recovery from jet lag, which highlights the potential of vasopressin signaling as a therapeutic target for management of circadian rhythm misalignment, such as jet lag and shift work.

http://www.sciencemag.org/content/342/6154/85.abstract