BRAIN POTENTIAL CHANGES AFTER INTRANASAL VS INTRAVENOUS ADMINISTRATION OF VASOPRESSIN - EVIDENCE FOR A DIRECT NOSE BRAIN PATHWAY FOR PEPTIDE EFFECTS IN HUMANS

There is evidence that intranasal application of peptides is a way to circumvent the blood-brain barrier, This led us to compare the effects of arginine-vasopressin (AVP) on event-related potentials (ERPs) in h ealthy men (n = 15) after intranasal and after intravenous (IV) admini stration. In a double-blind, crossover study, subjects received on thr ee different occasions 20 IU of AVP intranasally (IN), 1.5 IU of AVP I V, and saline solution, ERPs were recorded during the subject's perfor mance on an auditory attention task. Plasma concentrations of vasopres sin during task performance were enhanced after AVP, with the increase after IV administration of AVP exceeding that after intranasal AVP (p < 0.05). Intranasal administration of AVP substantially increased the P3 component of the ERP (p < 0.01), By contrast, IV administration of AVP had no consistent effects on the ERP responses. In supplementary experiments as well, IV administration of lower doses of AVP (0.1 and 0.025 IU) did not affect the ERP. Plasma vasopressin concentrations af ter the 0.025 IU dose in these experiments were comparable to those af ter intranasal administration of 20 IU AVP. The results provide functi onal evidence that in the human brain effects of peptides like AVP may be facilitated after IN as compared to IV administration.