Neurohypophyseal hormones manipulation modulate social and anxiety-related behavior in zebrafish
Oxytocin (OT) and arginine-vasopressin (AVP) regulate social behavior in mammals. Zebrafish (Danio rerio) allows higher throughput and ease in studying human brain disorders.
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.
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.
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.
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.
KeywordsOxytocin Vasopressin Isotocin Vasotocin Shoaling Anxiety Social behavior Selective antagonist
- Buske C, Gerlai R (2010) Shoaling develops with age in Zebrafish (Danio rerio). Prog Neuropsychopharmacol Biol Psychiatry. doi:10.1016/j.pnpbp.2010.09.003
- Gilchriest BJ, Tipping DR, Levy A, Baker BI (1998) Diurnal changes in the expression of genes encoding for arginine vasotocin and pituitary pro-opiomelanocortin in the rainbow trout (Oncorhynchus mykiss): correlation with changes in plasma hormones. J Neuroendocrinol 10:937–943PubMedCrossRefGoogle Scholar
- Griebel G, Simiand J, Serradeil-Le Gal C, Wagnon J, Pascal M, Scatton B, Maffrand JP, Soubrie P (2002) Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders. Proc Natl Acad Sci USA 99:6370–6375PubMedCrossRefGoogle Scholar
- Landgraf R, Frank E, Aldag JM, Neumann ID, Sharer CA, Ren X, Terwilliger EF, Niwa M, Wigger A, Young LJ (2003) Viral vector-mediated gene transfer of the vole V1a vasopressin receptor in the rat septum: improved social discrimination and active social behaviour. Eur J Neurosci 18:403–411PubMedCrossRefGoogle Scholar
- Sala M, Braida D, Lentini D, Busnelli M, Bulgheroni E, Capurro V, Finardi A, Donzelli A, Pattini L, Rubino TB et al (2011) Pharmacologic rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice: a neurobehavioral model of autism. Biol Psychiatry 69:875–882PubMedCrossRefGoogle Scholar
- Serradeil-Le Gal C, Raufaste D, Derick S, Blankenstein J, Allen J, Pouzet B, Pascal M, Wagnon J, Ventura MA (2007) Biological characterization of rodent and human vasopressin V1b receptors using SSR-149415, a nonpeptide V1b receptor ligand. Am J Physiol Regul Integr Comp Physiol 293:R938–R949PubMedCrossRefGoogle Scholar
- Sneckser JL, Ruhl N, Bauer K, McRobert SP (2010) The influence of sex and phenotype on shoaling decisions in zebra fish. Int J Comp Psychol 23:70–81Google Scholar
- Streisinger G (2000) The zebrafish book. Oregon Press, Eugene, OregonGoogle Scholar