title: CSF and blood oxytocin concentration changes following intranasal delivery in macaque.
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.
authors.affiliation: Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States of America; Department of Neuropsychology, University of Turin, Turin, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Dal Monte
authors.affiliation: Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Noble
authors.affiliation: Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Janita
authors.initials: J
authors.lastname: Turchi
authors.affiliation: Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Alex
authors.initials: A
authors.lastname: Cummins
authors.affiliation: Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Averbeck
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D010120:Oxytocics / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D010121:Oxytocin / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D010120:Oxytocics; D010121:Oxytocin