Oxytocin knockout mice: a model for studying stress-related and ingestive behaviours

Prog Brain Res. 2008;170:53-64. doi: 10.1016/S0079-6123(08)00405-6.


Oxytocin (OXT) that is released centrally is believed to be anxiolytic and have stress-attenuating effects. Oxytocin knockout (OXTKO) mice, a genetic model of OXT deficiency, have heightened corticosterone release after acute stress and greater anxiety-related behaviour in an elevated plus maze compared to wild-type (WT) mice. In the present set of experiments, we recorded the rise in body temperature, referred to as stress-induced hyperthermia (SIH), following transfer to a metabolic cage, which triggers both anxiety and corticosterone release in mice. SIH is a marker of activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system. Because corticosterone release after acute stress is typically greater in OXTKO than in WT mice, we measured SIH as a surrogate marker of corticosterone release. Following transfer to a metabolic cage, both OXTKO and WT mice increased body temperature, but to the same degree. Pregnant mice, which are known to have blunted corticosterone release to acute stress, had attenuated SIH after transfer to a metabolic cage compared to cycling mice, but both genotypes manifested the same degree of attenuation. In addition, we tested the effects of the cannabinoid receptor 1 (CBR1) antagonist/inverse agonist (AM251) upon feeding and SIH in OXTKO versus WT mice. CBR1 antagonists are known to diminish food intake and to enhance corticosterone both basally and following acute stress. Although AM251 blunted food intake, the effect was equivalent in both genotypes. The agent did not affect the SIH response compared to mice treated with vehicle. SIH is excellent for defining anxiolytic or blunted corticosterone responses (such as the stress hyporesponsiveness of pregnancy), but is limited in its ability to detect the heightened corticosterone responses that have been reported in OXTKO mice following exposure to psychogenic stress.

MeSH terms

  • Animals
  • Body Temperature
  • Corticosterone / metabolism*
  • Crosses, Genetic
  • Environment
  • Feeding Behavior / physiology*
  • Female
  • Fever / etiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxytocin / deficiency*
  • Oxytocin / genetics
  • Piperidines / pharmacology
  • Pregnancy
  • Pyrazoles / pharmacology
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Stress, Psychological / genetics*
  • Stress, Psychological / physiopathology


  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • AM 251
  • Oxytocin
  • Corticosterone