Abstract # 909 Event # 40:

Scheduled for Thursday, August 18, 2005 02:45 PM-03:15 PM: Session 6 (Crystal Ballroom) Oral Presentation

Female rhesus monkeys’ interest in infants and sexual behavior is reduced by peripherally administered non-peptide oxytocin antagonist, L368,899®

M. L. Boccia1, A. S. Goursaud2,3, J. Bachevalier2,3 and C. Pedersen1
1University of North Carolina at Chapel Hill, FPG Child Development Institute, Univ. of North Carolina at Chapel Hill, CB 8185, Chapel Hill, NC 27599-8185, USA, 2University of Texas at Houston, 3Emory University
     Research with non-primates has documented the role of oxytocin (OT) in maternal and sexual behavior, aggression and stress responses. The strongest experimental evidence that endogenous OT contributes to the expression of these behaviors is that central administration of OT antagonists inhibit maternal and sexual behaviors in non-primate species. While a few reports indicate that intracerebral ventricle administration of OT in monkeys increases some social behavior, no studies to date have assessed the effects of OT antagonist on primate behavior. Peptide OT antagonists used in rodents are less selective in primates and do not cross the blood brain barrier. We conducted studies using a Merck non-peptide antagonist selective for human uterine OT receptor, L368,899. To test if L368,899 penetrates the CNS, we administered 1 mg/kg IV and collected CSF samples after peripheral administration. L368,899 crossed the blood-brain barrier and was detectable in CSF. Second, we gave the same dose and brains were collected, dissected and assayed for L368,899. Accumulation was greatest in hypothalamus, septum, amygdala and hippocampus. Third, we tested interest in infants or sexual behavior after IV infusion of L368,899 or saline vehicle. In both behavioral tests, the OT antagonist reduced or eliminated the target behavior. These results are the first to directly implicate endogenous OT in activation of primate maternal and sexual behavior. This research was supported by MH06691 (MLB) and HD35471 and NAAR (JB).