Intranasal Application of Vasopressin Fails to Elicit Changes in Brain Immediate Early Gene Expression, Neural Activity and Behavioural Performance of Rats

Intranasal administration has been widely used to investigate the effects of the neuropeptides vasopressin and oxytocin on human behaviour and neurological disorders, although exactly what happens when these neuropeptides are administered intranasally is far from clear. In particular, it is not clear whether a physiological significant amount of peptide enters the brain to account for the observed effects. In the present study, we investigated whether the intranasal administration of vasopressin and oxytocin to rats induces the expression of the immediate-early gene product Fos in brain areas that are sensitive to centrally-administered peptide, whether it alters neuronal activity in the way that centrally-administered peptide does, and whether it affects behaviour in the ways that are expected from studies of centrally-administered peptide. We found that, whereas i.c.v. injection of very low doses of vasopressin or oxytocin increased Fos expression in several distinct brain regions, intranasal administration of large doses of the peptides had no significant effect. By contrast to the effects of vasopressin applied topically to the main olfactory bulb, we saw no changes in the electrical activity of olfactory bulb mitral cells after intranasal vasopressin administration. In addition, vasopressin given intranasally had no significant effects on social recognition or short-term recognition memory. Finally, intranasal infusions of vasopressin had no significant effects on the parameters monitored on the elevated plus maze, a rodent model of anxiety. Our data obtained in rats suggest that, after intranasal administration, significant amounts of vasopressin and oxytocin do not reach areas in the brain at levels sufficient to change immediate early gene expression, neural activity or behaviour in the ways described for central administration of the peptides.