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The Journal of Neuroscience, January 2, 2008, 28(1):228-238; doi:10.1523/JNEUROSCI.3490-07.2008
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Behavioral/Systems/Cognitive
Vasopressin Increases Locomotion through a V1a Receptor in Orexin/Hypocretin Neurons: Implications for Water Homeostasis
Tomomi Tsunematsu,1 Li-Ying Fu,2 Akihiro Yamanaka,1,2 Kanako Ichiki,1 Akito Tanoue,3 Takeshi Sakurai,1 andAnthony N. van den Pol2 1Department of Molecular Pharmacology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan, 2Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut 06520, and 3Department of Pharmacology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
Before Feb. 1, 2008, correspondence should be addressed to Dr. Akihiro Yamanaka, Department of Molecular Pharmacology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan, Email: yamank{at}md.tsukuba.ac.jp; after Feb. 1, 2008, correspondence should be addressed to Dr. Akihiro Yamanaka, Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higasiyama Myodaiji, Okazaki 444-8787, Japan, Email: yamank{at}dg8.so-net.ne.jp
Water homeostasis is a critical challenge to survival for land mammals. Mice display increased locomotor activity when dehydrated, a behavior that improves the likelihood of locating new sources of water and simultaneously places additional demands on compromised hydration levels. The neurophysiology underlying this well known behavior has not been previously elucidated. We report that the anti-diuretic hormone arginine-vasopressin (AVP) is involved in this response. AVP and oxytocin directly induced depolarization and an inward current in orexin/hypocretin neurons. AVP-induced activation of orexin neurons was inhibited by a V1a receptor (V1aR)-selective antagonist and was not observed in V1aR knock-out mice, suggesting an involvement of V1aR. Subsequently activation of phospholipase Cβ triggers an increase in intracellular calcium by both calcium influx through nonselective cation channels and calcium release from calcium stores in orexin neurons. Intracerebroventricular injection of AVP or water deprivation increased locomotor activity in wild-type mice, but not in transgenic mice lacking orexin neurons. V1aR knock-out mice were less active than wild-type mice. These results suggest that the activation of orexin neurons by AVP or oxytocin has an important role in the regulation of spontaneous locomotor activity in mice. This system appears to play a key role in water deprivation-induced hyperlocomotor activity, a response to dehydration that increases the chance of locating water in nature.
Key words: orexin; hypocretin; patch clamp; vasopressin; V1a receptor; water deprivation
Received Aug. 1, 2007; revised Oct. 9, 2007; accepted Oct. 30, 2007.
Before Feb. 1, 2008, correspondence should be addressed to Dr. Akihiro Yamanaka, Department of Molecular Pharmacology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan, Email: yamank{at}md.tsukuba.ac.jp; after Feb. 1, 2008, correspondence should be addressed to Dr. Akihiro Yamanaka, Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higasiyama Myodaiji, Okazaki 444-8787, Japan, Email: yamank{at}dg8.so-net.ne.jp
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