CSF and Blood Oxytocin Concentration Changes following Intranasal Delivery in Macaque

被引:137
作者
Dal Monte, Olga [1 ,2 ]
Noble, Pamela L. [1 ]
Turchi, Janita [1 ]
Cummins, Alex [1 ]
Averbeck, Bruno B. [1 ]
机构
[1] NIH, NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA
[2] Univ Turin, Dept Neuropsychol, Turin, Italy
关键词
CEREBROSPINAL-FLUID; PLASMA OXYTOCIN; SPINAL-CORD; BRAIN; VASOPRESSIN; NASAL; RADIOIMMUNOASSAY; PATHWAYS; BEHAVIOR; RHYTHM;
D O I
10.1371/journal.pone.0103677
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:6
相关论文
共 48 条
[1]   PATTERN OF OXYTOCIN CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL-FLUID OF LACTATING RHESUS-MONKEYS (MACACA-MULATTA) - EVIDENCE FOR FUNCTIONALLY INDEPENDENT OXYTOCINERGIC PATHWAYS IN PRIMATES [J].
AMICO, JA ;
CHALLINOR, SM ;
CAMERON, JL .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1990, 71 (06) :1531-1535
[2]   A TIME-DEPENDENT PEAK OF OXYTOCIN EXISTS IN CEREBROSPINAL-FLUID BUT NOT IN PLASMA OF HUMANS [J].
AMICO, JA ;
TENICELA, R ;
JOHNSTON, J ;
ROBINSON, AG .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1983, 57 (05) :947-951
[3]   Vasopressin administration modulates anxiety-related behavior in rats [J].
Appenrodt, E ;
Schnabel, R ;
Schwarzberg, H .
PHYSIOLOGY & BEHAVIOR, 1998, 64 (04) :543-547
[4]  
ARTMAN HG, 1982, J NEUROSCI, V2, P598
[5]   Sniffing neuropeptides: a transnasal approach to the human brain [J].
Born, J ;
Lange, T ;
Kern, W ;
McGregor, GP ;
Bickel, U ;
Fehm, HL .
NATURE NEUROSCIENCE, 2002, 5 (06) :514-516
[6]   Brain oxytocin correlates with maternal aggression: Link to anxiety [J].
Bosch, OJ ;
Meddle, SL ;
Beiderbeck, DI ;
Douglas, AJ ;
Neumann, ID .
JOURNAL OF NEUROSCIENCE, 2005, 25 (29) :6807-6815
[7]   DEVELOPMENT OF A RADIOIMMUNOASSAY FOR OXYTOCIN - EXTRACTION OF OXYTOCIN FROM URINE AND DETERMINATION OF EXCRETION RATE FOR EXOGENOUS AND ENDOGENOUS OXYTOCIN IN HUMAN URINE [J].
BOYD, NRH ;
CHARD, T ;
JACKSON, DB ;
FORSLING, ML ;
HOLLINGSWORTH, S .
JOURNAL OF ENDOCRINOLOGY, 1972, 52 (01) :59-+
[8]   The acute effects of intranasal oxytocin administration on endocrine and sexual function in males [J].
Burri, Andrea ;
Heinrichs, Markus ;
Schedlowski, Manfred ;
Kruger, Tillmann H. C. .
PSYCHONEUROENDOCRINOLOGY, 2008, 33 (05) :591-600
[9]   Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques (Macaca mulatta) [J].
Chang, Steve W. C. ;
Barter, Joseph W. ;
Ebitz, R. Becket ;
Watson, Karli K. ;
Platt, Michael L. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (03) :959-964
[10]  
Chen Xue-Qing, 1998, J Alzheimers Dis, V1, P35