title: Neurohypophyseal hormones manipulation modulate social and anxiety-related behavior in zebrafish.
abstract: BACKGROUND
  Oxytocin (OT) and arginine-vasopressin (AVP) regulate social behavior in mammals. Zebrafish (Danio rerio) allows higher throughput and ease in studying human brain disorders.
  
  
  OBJECTIVE
  This study investigated in zebrafish the effect of non-mammalian homologs isotocin (IT) and vasotocin (AVT) in comparison with OT/AVP on social behavior and fear response to predator. The mechanism was studied using the most human selective OT and AVP receptor antagonists.
  
  
  METHODS
  Zebrafish were injected i.m. with increasing doses (0.001-40 ng/kg) of the neuropeptides. DesGly-NH(2)-d(CH(2))(5)-[D-Tyr(2),Thr(4)]OVT) for OT receptor, SR 49059 for V1a subtype receptor, and SSR-149415 for V1b subtype receptor were injected i.m. 10 min before each agonist.
  
  
  RESULTS
  All the peptides increased social preference and reduced fear to predator response in a dose-dependent manner interpolated by symmetrical parabolas. AVT/AVP were more potent to elicit anxiolytic than social effect while IT and OT were equally potent. All the antagonists dose-dependently inhibited both the effects induced by the neuropeptides. The ratio between the ED50 obtained for blocking the OT-induced effects on social preference and fear response to predator was very high only for desglyDTTyrOVT (160). SR49059 showed the highest ratio in blocking AVP-induced effects (807). The less selective antagonist appeared to be SSR149415.
  
  
  CONCLUSIONS
  For the first time, IT/AVT and OT/AVP were found to modulate in zebrafish, social behavior, unrelated to sex, and fear to predator response through at least two different receptors. Zebrafish is confirmed as a valid, reliable model to study deficit in social behavior characteristic of some psychiatric disorders.
authors.affiliation: Department of Pharmacology, Chemotherapy and Medical Toxicology, Università degli Studi di Milano, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Braida
authors.forename: Andrea
authors.initials: A
authors.lastname: Donzelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Martucci
authors.forename: Valeria
authors.initials: V
authors.lastname: Capurro
authors.forename: Marta
authors.initials: M
authors.lastname: Busnelli
authors.forename: Bice
authors.initials: B
authors.lastname: Chini
authors.forename: Mariaelvina
authors.initials: M
authors.lastname: Sala
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D065092:Antidiuretic Hormone Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D009951:Ornipressin / Q000031:analogs & derivatives / Q000494:pharmacology; D010121:Oxytocin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D010909:Pituitary Hormones, Posterior / Q000494:pharmacology / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology; D011869:Radioligand Assay / Q000379:methods / Q000706:statistics & numerical data; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000502:physiology; D017483:Receptors, Vasopressin / Q000502:physiology*; D012919:Social Behavior; D013550:Swimming; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D014668:Vasotocin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D015027:Zebrafish
chemical_list: C456029:1-(5-chloro-1-((2,4-dimethoxyphenyl)sulfonyl)-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide; D014151:Anti-Anxiety Agents; D065092:Antidiuretic Hormone Receptor Antagonists; D007211:Indoles; D010909:Pituitary Hormones, Posterior; D011759:Pyrrolidines; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D014667:Vasopressins; C074541:vasotocin, desGly(NH2)(9)d(CH2)5-Tyr(Me)(2)-Thr(4)-Orn(8)-; D009951:Ornipressin; D010121:Oxytocin; C008215:isotocin; C082134:relcovaptan; D014668:Vasotocin