Brain potential changes after intranasal vs. intravenous administration of vasopressin: evidence for a direct nose-brain pathway for peptide effects in humans

• Published in: Biological psychiatry (1969) Vol. 39; no. 5; pp. 332 - 340
• Main Authors: Pietrowsky, Reinhard, Strüben, Christel, Mölle, Matthias, Fehm, Horst L., Born, Jan
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.1996; Elsevier Science
• Subjects: Administration, Intranasal; Adult; Arginine Vasopressin - administration & dosage; Arginine Vasopressin - blood; Arginine Vasopressin - pharmacology; Arginine-vasopressin; Arousal - drug effects; Arousal - physiology; Attention - drug effects; Attention - physiology; Biological and medical sciences; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Cross-Over Studies; Double-Blind Method; Electroencephalography - drug effects; ERPs; event-related potentials; Evoked Potentials, Auditory - drug effects; Evoked Potentials, Auditory - physiology; Hormones. Endocrine system; human; Humans; Injections, Intravenous; Male; Medical sciences; Nasal Mucosa - innervation; Neural Pathways - drug effects; Neural Pathways - physiology; Neuropeptides - administration & dosage; Neuropeptides - blood; Neuropeptides - pharmacology; nose-brain pathway; Pharmacology. Drug treatments; Pitch Discrimination - drug effects; Pitch Discrimination - physiology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; ERPs; nose-brain pathway; P3; event-related potentials; human; Arginine-vasopressin; Human; Acoustic stimulus; Intravenous administration; Neurohypophyseal hormone; Electrophysiology; Route of administration; Neuropeptide; Event evoked potential; Intranasally administration; Biological activity; Comparative study; Vasopressin
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/0006-3223(95)00180-8

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 healthy men ( n = 15) after intranasal and after intravenous (IV) administration. In a double-blind, crossover study, subjects received on three different occasions 20 IU of AVP intranasally (IN), 1.5 IU of AVP IV, and saline solution. ERPs were recorded during the subject's performance on an auditory attention task. Plasma concentrations of vasopressin 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 after the 0.025 IU dose in these experiments were comparable to those after intranasal administration of 20 IU AVP. The results provide functional evidence that in the human brain effects of peptides like AVP may be facilitated after IN as compared to IV administration.