Oral Presentation The International Congress of Neuroendocrinology 2014

Effects of chronic central oxytocin infusion under basal and chronic stress conditions: Are we ready for its therapeutic use? (#11)

Inga Neumann 1
  1. University of Regensburg, Regensburg, Germany

Brain oxytocin (OXT) has been shown to exert anxiolytic and pro-social effects, and to inhibit the activity of the HPA axis. We have recently shown that OXT promotes social preference behaviour and prevents social phobia induced by social defeat in rats and mice1. Further, in a mouse paradigm for social fear conditioning2, OXT specifically reversed social fear – an effect which was localized within the dorsolateral septum, where social fear was associated with reduced OXT receptor (OXTR) binding and blunted local OXT release. The acute anxiolytic effects of OXT are mediated via activation of hypothalamic OXT receptors (OXTR), which are GPCR, and subsequently of the MAPK pathway.

However, in order to establish OXT as a potential psychotherapeutic option, effects of chronic neuropeptide treatment need to be studied. Chronic icv infusion of OXT over 2 weeks using osmotic minipumps dose-dependently increased anxiety-related behaviour and reduced OXTR binding within relevant brain regions3.  However, in a mouse model of chronic psychosocial stress, i.e. chronic subordinate colony housing (CSC) over 3 weeks, the lower dose of chronic OXT (1 ng/h) attenuated or even prevented various adverse stress effects on immunological, physiological and emotional parameters such as increased anxiety3. These results further support its stress-protective properties. Thus, given both negative, but also beneficial effects seen after chronic central OXT infusion, a deeper understanding of long-lasting effects is required before OXT can be considered for long-term therapeutic use for the treatment of adolescent or adult patients suffering from psychopathologies, such as autism, schizophrenia or anxiety-disorders.

Supported by DFG, EU and BMBF.

  1. Toth I, et al. 2012 Neuropsychopharmacology 37:1433-43 2. Lukas M et al. (2011) Neuropsychopharmacology 36:2159-68 3. Peters S et al., Psychoneuroendocrinology (in press)