The oxytocin system in drug discovery for autism: animal models and novel therapeutic strategies

Horm Behav. 2012 Mar;61(3):340-50. doi: 10.1016/j.yhbeh.2011.12.010. Epub 2011 Dec 20.


Animal models and behavioral paradigms are critical for elucidating the neural mechanism involved in complex behaviors, including social cognition. Both genotype and phenotype based models have implicated the neuropeptide oxytocin (OT) in the regulation of social behavior. Based on the findings in animal models, alteration of the OT system has been hypothesized to play a role in the social deficits associated with autism and other neuropsychiatric disorders. While the evidence linking the peptide to the etiology of the disorder is not yet conclusive, evidence from multiple animal models suggest modulation of the OT system may be a viable strategy for the pharmacological treatment of social deficits. In this review, we will discuss how animal models have been utilized to understand the role of OT in social cognition and how those findings can be applied to the conceptualization and treatment of the social impairments in ASD. Animal models with genetic alterations of the OT system, like the OT, OT receptor and CD38 knock-out mice, and those with phenotypic variation in social behavior, like BTBR inbred mice and prairie voles, coupled with behavioral paradigms with face and construct validity may prove to have predictive validity for identifying the most efficacious methods of stimulating the OT system to enhance social cognition in humans. The widespread use of strong animal models of social cognition has the potential yield pharmacological, interventions for the treatment social impairments psychiatric disorders. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Administration, Intranasal
  • Animals
  • Anxiety / psychology
  • Arvicolinae
  • Autistic Disorder / drug therapy*
  • Autistic Disorder / genetics*
  • Autistic Disorder / therapy
  • Behavior Therapy
  • Cystinyl Aminopeptidase / antagonists & inhibitors
  • Disease Models, Animal
  • Drug Discovery*
  • Genotype
  • Humans
  • Mice
  • Models, Psychological
  • Oxytocin / administration & dosage
  • Oxytocin / genetics
  • Oxytocin / physiology*
  • Oxytocin / therapeutic use
  • Phenotype
  • Receptors, Oxytocin / agonists
  • Recognition, Psychology / physiology
  • Social Behavior


  • Receptors, Oxytocin
  • Oxytocin
  • Cystinyl Aminopeptidase