Vasopressin increases locomotion through a V1a receptor in orexin/hypocretin neurons: Implications for water homeostasis

Tomomi Tsunematsu, Li Ying Fu, Akihiro Yamanaka, Kanako Ichiki, Akito Tanoue, Takeshi Sakurai, Anthony N. Van Den Pol

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)228-238
Number of pages11
JournalJournal of Neuroscience
Issue number1
Publication statusPublished - 2008 Jan 2
Externally publishedYes


  • Hypocretin
  • Orexin
  • Patch clamp
  • V1a receptor
  • Vasopressin
  • Water deprivation

ASJC Scopus subject areas

  • Neuroscience(all)


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