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Abstract
Oxytocin (OT) in the central nervous system (CNS) influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.
Highlights
Oxytocin (OT) is a nonapeptide characterized by a six amino acid ring structure with a three amino acid tail
Because there was no main effect of delivery method, we collapsed them together to confirm the significant increase of OT in cerebral spinal fluid (CSF) after OT administration compared to saline, and analyzed differences between pre- and post- OT and saline administration
We found that CSF OT levels were significantly elevated 40 minutes after delivery relative to baseline when OT was administered (t(14) = 4.4, p = .004) but not when saline was administered (t(14) = .71, p = 1)
Summary
Oxytocin (OT) is a nonapeptide characterized by a six amino acid ring structure with a three amino acid tail. This molecule is too large to cross the blood–brain barrier (BBB) [1,2]. Studies have shown that intranasal administration of OT in humans influences social information processing, with effects at both behavioral and neural levels [7]. OT has been shown to modulate amygdala activity in response to threatening social stimuli [14], pain [15], and emotional faces [16]
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