The neuropeptide oxytocin (OXT) has been shown to affect various aspects of emotionality and stress responsiveness both in animal and human studies. In rats, OXT acts as an endogenous anxiolytic and exerts an inhibitory effect on the responsiveness of the HPA axis to emotional and physical stressors (1-3). Sites of action within the rat brain include the olfactory bulb (4), the septum and the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Its potential therapeutic use is limited due to its restricted access to the brain via the blood-brain barrier. In a series of preliminary studies, the hypothesis that OXT applied intranasally" (i.n.) (i) gets access to the olfactory bulb, (ii) triggers local noradrenaline release, (iii) affects the firing rate of antidromically identified neurons of the SON, and (iv) alters various aspects of emotional behavior in rats bred for high anxiety related behavior (5) was tested.

Following i.n. OXT the peak concentration in plasma was reached after 50-80 min whereas, in the same male rats, microdialysis of the olfactory bulb revealed the OXT peak already 20 min p.a. In this brain area, the release of noradrenaline tended to be increased in response to i.n. OXT, but not vehicle.

In female rats, i.n. OXT increased the firing rate of SON neurons within 2 to 12 min, whereas application of vehicle had no effect in most cells tested. In male hyper-anxious rats, i.n. OXT applied 15 min before testing exerted an anxiolytic effect on the elevated plus-maze and altered the stress-coping strategy towards higher activity in the forced swim test compared to vehicle treatment. In lactating rats, i.n. OXT reduced the maternal aggressive behavior in the maternal defense test.

These results provide the first indication that OXT applied via this route gets rapid access to the brain and modulates neuronal functions within both the olfactory bulb and the hypothalamus. Further, the anxiolytic, anti-depressive and anti-aggressive effects described after i.n. OXT make this route of administration potentially interesting for therapeutic use.

1) Windle et al., 1997, Endocrinology 138:2829-2834
2) Neumann et al.. 2000, J.Neuroendocrinol. 12: 235-243
3) Neumann et al., 2000, Neuroscience 95: 567-575.
4) Dluzen et al., 1999, Eur. J.Neurosci. 12: 760-766
5) Landgraf et al., 1999, J. Neuroendocrinoi. 11: 405-407