Intranasal oxytocin in a genetic animal model of autism

Abstract

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly characterized by deficient sociability and repetitive behaviors. Effective treatment for the core symptoms of ASD is still lacking. Behavioral interventions show limited effectiveness, while pharmacotherapy focuses on the amelioration of secondary symptomatology. Oxytocin (OXT) is a neuropeptide known for its prosocial impact, making it a candidate drug for ASD treatment. Its alleviating effect has been and still is widely researched, but outcomes reported by clinical studies are ambiguous. We examined the effect of daily intranasal OXT (0.8 IU/kg) administration for 4 weeks on the ASD-like phenotype in Shank3^-/- adult mice. Animals treated with OXT spent twice as much time interacting with the social partner as early as after 2 weeks of treatment. Furthermore, OXT-treated mice exhibited reduced explorative behavior by 50%, after 4 weeks of treatment, and a 30% reduction in repetitive behavior, 4 weeks after treatment termination. One-fold higher sociability and 30% reduced exploration due to OXT lasted up to 4 weeks following the treatment termination. However, social disinterest was elevated by roughly 10% as well, indicating a form of social ambivalence. Obtained results support the therapeutic potential of intranasally administered OXT in alleviating social shortfalls in a genetic model of ASD. Subsequent research is necessary to elucidate the benefits and risks of the long-term OXT administration, as well as its applicability in other ASD models and the potential treatment effect on social communication, which was not measured in the present study.

Fig. 1. The effect of intranasal oxytocin on sociability.

A Cumulative time spent socially interacting with a social-partner mouse in Reciprocal interaction test. B Cumulative time spent without interest in social contact with a social-partner mouse in Reciprocal interaction test. * 0.05; **/## p < 0.01; ***/### p < 0.001.

Fig. 2. The effect of intranasal oxytocin on repetitive and explorative behavior.

A. Cumulative time spent self-grooming in the Open field test. B. Cumulative time spent rearing in Open field test. */# p < 0.05; **/## p < 0.01; ***/### p < 0.001.

Fig. 3. The effect of oxytocin treatment on anxiety-like behavior, locomotor activity and body weight.

A Cumulative time spent in the center zone in the Open field test. B Cumulative distance traveled in Open field test. C. Body weight.