Oral Presentation The International Congress of Neuroendocrinology 2014

The development of the mouse oxytocin system: potential organizational effects on behavior (#86)

Heather K Caldwell 1 , Steven Tamborski 1
  1. Kent State University, Kent, OH, United States

Recent studies suggest that the neuropeptide oxytocin (Oxt) may be important for organizing the neural circuitry that regulates adult male aggressive behavior. Specifically, male Oxt knockout (Oxt -/-) mice born to null mutant dams have heightened aggressive behavior in adulthood, which cannot be mitigated by cross-fostering to C57BL/6J females. Likewise, male Oxt receptor knockout (Oxtr -/-) mice that lack Oxt signaling during development also have heightened levels of aggressive behavior in adulthood. These data contrast with that from male forebrain specific Oxtr knockout mice, in which the Oxtr gene is excised 21-28 days after birth and have normal male aggressive behavior.  Based on these data it has been hypothesized that fetal exposure to Oxt is necessary for normal displays of aggressive behavior in adulthood. To understand where and when Oxt may be acting during fetal development, we determined the initial expression of mouse Oxt and Oxtr mRNA as well as Oxtr protein. We then performed a transuterine injection of an oxytocin antagonist (OTA), to determine when in embryonic development Oxt affects adult intermale aggression. Results indicate that Oxtr mRNA was present at least by embryonic day 12 (E12) for both sexes. We observed a sex difference for Oxt mRNA with initial expression on E16 in females and on postnatal day 2 in males. By E16 the Oxtr was available for binding within the ventricular and subventricular zone as well as the amygdala, a region thought to modulate aggression. Preliminary data from the transuterine injection of the OTA suggests that E14 injected mice may have increased adult intermale aggressive behavior. Because male Oxt mRNA expression is later than Oxtr peptide expression, it may be that maternal Oxt acts on the Oxtr in the fetal brain to organize the neural circuitry that underlies intermale aggressive behavior.