Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism

PLoS One. 2019 Jan 10;14(1):e0210389. doi: 10.1371/journal.pone.0210389. eCollection 2019.


Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impaired social interactions, difficulty with communication, and repetitive behavior patterns. In humans affected by ASD, there is a male pre-disposition towards the condition with a male to female ratio of 4:1. In part due to the complex etiology of ASD including genetic and environmental interplay, there are currently no available medical therapies to improve the social deficits of ASD. Studies in rodent models and humans have shown promising therapeutic effects of oxytocin in modulating social adaptation. One pharmacological approach to stimulating oxytocinergic activity is the melanocortin receptor 4 agonist Melanotan-II (MT-II). Notably the effects of oxytocin on environmental rodent autism models has not been investigated to date. We used a maternal immune activation (MIA) mouse model of autism to assess the therapeutic potential of MT-II on autism-like features in adult male mice. The male MIA mice exhibited autism-like features including impaired social behavioral metrics, diminished vocal communication, and increased repetitive behaviors. Continuous administration of MT-II to male MIA mice over a seven-day course resulted in rescue of social behavioral metrics. Normal background C57 male mice treated with MT-II showed no significant alteration in social behavioral metrics. Additionally, there was no change in anxiety-like or repetitive behaviors following MT-II treatment of normal C57 mice, though there was significant weight loss following subacute treatment. These data demonstrate MT-II as an effective agent for improving autism-like behavioral deficits in the adult male MIA mouse model of autism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autistic Disorder / drug therapy*
  • Behavior, Animal / drug effects
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peptides, Cyclic / therapeutic use*
  • Receptor, Melanocortin, Type 4 / metabolism
  • Receptor, Melanocortin, Type 4 / physiology
  • Social Behavior
  • alpha-MSH / analogs & derivatives*
  • alpha-MSH / therapeutic use


  • MC4R protein, mouse
  • Peptides, Cyclic
  • Receptor, Melanocortin, Type 4
  • melanotan-II
  • alpha-MSH

Grant support

EM received funding from the UCLA Children's Discovery and innovation Institute William F. Friedman Fellowship Grant. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.