Neurohypophyseal hormones manipulation modulate social and anxiety-related behavior in zebrafish

Source: Psychopharmacology

Abstract
Rationale  
Oxytocin (OT) and arginine-vasopressin (AVP) regulate social behavior in mammals. Zebrafish (Danio rerio) allows higher throughput and ease in studying human brain disorders.

Objectives  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-NH2-d(CH2)5-[d-Tyr2,Thr4]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.

  • Content Type Journal Article
  • Category Original Investigation
  • Pages 1-12
  • DOI 10.1007/s00213-011-2482-2
  • Authors
    • Daniela Braida, Department of Pharmacology, Chemotherapy and Medical Toxicology, Università degli Studi di Milano, Milan, Italy
    • Andrea Donzelli, Department of Pharmacology, Chemotherapy and Medical Toxicology, Università degli Studi di Milano, Milan, Italy
    • Roberta Martucci, Department of Pharmacology, Chemotherapy and Medical Toxicology, Università degli Studi di Milano, Milan, Italy
    • Valeria Capurro, Department of Pharmacology, Chemotherapy and Medical Toxicology, Università degli Studi di Milano, Milan, Italy
    • Marta Busnelli, Department of Pharmacology, Chemotherapy and Medical Toxicology, Università degli Studi di Milano, Milan, Italy
    • Bice Chini, CNR, Institute of Neuroscience, Via Vanvitelli 32, Milan, Italy
    • Mariaelvina Sala, Department of Pharmacology, Chemotherapy and Medical Toxicology, Università degli Studi di Milano, Milan, Italy

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