Administration of Atosiban, an oxytocin receptor antagonist, ameliorates autistic-like behaviors in a female rat model of valproic acid-induced autism.

Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 8004872 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7549 (Electronic) Linking ISSN: 01664328 NLM ISO Abbreviation: Behav Brain Res Subsets: MEDLINE

Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.

Valproic Acid*/pharmacology ; Receptors, Oxytocin*/antagonists & inhibitors ; Receptors, Oxytocin*/metabolism ; Disease Models, Animal* ; Oxytocin*/pharmacology ; Oxytocin*/metabolism ; Oxytocin*/administration & dosage ; Vasotocin*/analogs & derivatives ; Vasotocin*/pharmacology ; Autistic Disorder*/chemically induced ; Autistic Disorder*/drug therapy; Animals ; Female ; Rats ; Prefrontal Cortex/drug effects ; Prefrontal Cortex/metabolism ; Autism Spectrum Disorder/chemically induced ; Autism Spectrum Disorder/drug therapy ; Hippocampus/drug effects ; Hippocampus/metabolism ; Behavior, Animal/drug effects ; Rats, Sprague-Dawley ; Neuronal Plasticity/drug effects ; Social Interaction/drug effects ; Sexual Behavior, Animal/drug effects ; Anxiety/drug therapy ; Anxiety/chemically induced ; Pregnancy

Autism spectrum disorder (ASD) is a pervasive developmental disorder with gender differences. Oxytocin (OXT) is currently an important candidate drug for autism, but the lack of data on female autism is a big issue. It has been reported that the effect of OXT is likely to be different between male and female ASD patients. In the study, we specifically explored the role of the OXT signaling pathway in a VPA-induced female rat's model of autism. The data showed that there was an increase of either oxytocin or its receptor expressions in both the hippocampus and the prefrontal cortex of VPA-induced female offspring. To determine if the excess of OXT signaling contributed to autism symptoms in female rats, exogenous oxytocin and oxytocin receptor antagonists Atosiban were used in the experiment. It was found that exogenous oxytocin triggered autism-like behaviors in wild-type female rats by intranasal administration. More interestingly, several autism-like deficits including social interaction, anxiety, and repeat stereotypical sexual behavior in the VPA female offspring were significantly attenuated by oxytocin receptor antagonists Atosiban. Moreover, Atosiban also effectively improved the synaptic plasticity impairment induced by VPA in female offspring. Our results suggest that oxytocin receptor antagonists significantly improve autistic-like behaviors in a female rat model of valproic acid-induced autism.
Competing Interests: Competing interests The authors declare that they have no competing interests.
(Copyright © 2024 Elsevier B.V. All rights reserved.)

Keywords: Autism; Female; Oxytocin; Oxytocin receptor antagonists; Valproic acid

614OI1Z5WI (Valproic Acid)
0 (Receptors, Oxytocin)
081D12SI0Z (atosiban)
50-56-6 (Oxytocin)
W6S6URY8OF (Vasotocin)

Date Created: 20240523 Date Completed: 20240606 Latest Revision: 20240614

20240614

10.1016/j.bbr.2024.115052

38782096