Evidence for intranasal oxytocin delivery to the brain: recent advances and future perspectives
The neuropeptide oxytocin plays an evolutionarily conserved role in mammalian social behavior. To experimentally manipulate central levels of oxytocin, animal studies have adopted direct intracerebroventricular (ICV) delivery to the brain, given that only small amounts of peripherally circulating oxytocin are thought to transfer from the periphery to the central compartment. Despite striking effects on social behavior in animals, ICV drug delivery is largely impractical for human therapies. Intranasal oxytocin delivery provides a non-invasive alternative to increase central oxytocin activity, and has shown promise as a treatment for psychiatric illnesses characterized by social dysfunction. Intranasal oxytocin delivery is purported to increase central oxytocin concentrations via channels surrounding trigeminal and olfactory nerve fibres, which may facilitate increased activity at central oxytocin receptors. This review outlines the evidence for intranasal oxytocin delivery increasing central concentrations or activity, identifies current knowledge gaps, and highlights future research opportunities. Recent efforts to enhance intranasal oxytocin delivery via improved intranasal delivery technology and dose-ranging studies are also discussed.