title: Vasopressin increases locomotion through a V1a receptor in orexin/hypocretin neurons: implications for water homeostasis.
abstract: 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 Cbeta 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.
authors.affiliation: Department of Molecular Pharmacology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Tsunematsu
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Fu
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamanaka
authors.forename: Kanako
authors.initials: K
authors.lastname: Ichiki
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakurai
authors.forename: Anthony N
authors.initials: AN
authors.lastname: van den Pol
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D050034:Antidiuretic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008124:Locomotion / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics; D000068797:Orexins; D010121:Oxytocin / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D017483:Receptors, Vasopressin / Q000172:deficiency / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology*; D014868:Water Deprivation / Q000502:physiology
chemical_list: D050034:Antidiuretic Agents; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D017483:Receptors, Vasopressin; D014667:Vasopressins; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; D010121:Oxytocin; D002118:Calcium