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Author Notes:

Direct correspondence to: Maria L. Boccia, Ph.D., FPG Child Development Institute, University of North Carolina at Chapel Hill, Chapel Hill NC 27599-8185, phone: 919-966-0022, fax: 919-8435784, email: maria_boccia@unc.edu

We would like to thank Dr. Christian Newcomer for making the animals available for the pharmacokinetic studies and for assisting with the studies by performing anesthesia, euthanasia, and CSF collection procedures, Dr. Gary Duncan for performing the brain dissections, and Dr. Doug Pettibone for providing the L368,899.

Subjects:

Research Funding:

This research was supported by PHS grants MH06691 to MLB, and HD35471 and NAAR to JB.

Keywords:

  • Amygdala
  • Animals
  • Blood-Brain Barrier
  • Bornanes
  • Female
  • Frontal Lobe
  • Hippocampus
  • Hormone Antagonists
  • Hypothalamus
  • Limbic System
  • Macaca mulatta
  • Male
  • Maternal Behavior
  • Oxytocin
  • Piperazines
  • Septum of Brain
  • Sexual Behavior, Animal

Peripherally administered non-peptide oxytocin antagonist, L368,899®, accumulates in limbic brain areas: A new pharmacological tool for the study of social motivation in non-human primates

Tools:

Journal Title:

Hormones and Behavior

Volume:

Volume 52, Number 3

Publisher:

, Pages 344-351

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Central administration of oxytocin (OT) antagonists inhibits maternal and sexual behavior in non-primates, providing the strongest experimental evidence that endogenous OT facilitates these behaviors. While there have been a few reports that ICV administration of OT increases social behaviors in monkeys, no studies to date have assessed the effects of OT antagonists. Therefore, we studied in rhesus monkeys whether L368,899®, a non-peptide antagonist produced by Merck that selectively blocks the human uterine OT receptor, penetrates the CNS after peripheral administration and alters female maternal and sexual behavior. In two studies in four male monkeys, L368,899 was injected iv (1 mg/kg) after which (1) CSF samples were collected at intervals over 4 h and (2) brains were collected at 60 min. Assay of samples confirmed that iv-administered L368,899 entered CSF and accumulated in the hypothalamus, septum, orbitofrontal cortex, amygdala and hippocampus, but not other areas. An adult female monkey was tested for interest in either an infant or sexual behavior, receiving a different iv treatment prior to each test (1 or 3 mg/kg of L368,899 or saline). OT antagonist treatment reduced or eliminated interest in the infant and sexual behavior. These results, although preliminary, are the first to directly implicate endogenous OT in activation of primate maternal interest and sexual behavior. While it remains to be empirically demonstrated that peripherally administered L368,899 blocks central OT receptors, our behavioral findings suggest that this non-peptide antagonist may facilitate testing OT involvement in a variety of social and other behaviors in primates. © 2007 Elsevier Inc. All rights reserved.

Copyright information:

© 2007 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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