Sex differences in the neural and behavioral response to intranasal oxytocin and
vasopressin during human social interaction.
Author(s): Rilling JK(1), Demarco AC, Hackett PD, Chen X, Gautam P, Stair S, Haroon E,
Thompson R, Ditzen B, Patel R, Pagnoni G.
Affiliation(s): Author information:
(1)Department of Anthropology, Emory University, United States; Department of
Psychiatry and Behavioral Sciences, Emory University, United States; Center for
Behavioral Neuroscience, Emory University, United States; Yerkes National Primate
Research Center, Emory University, United States; Center for Translational Social
Neuroscience, Emory University, United States. Electronic address:
jrillin@emory.edu.
Publication date & source: 2014, Psychoneuroendocrinology. , 39:237-48
Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior,
and dysfunction in both systems has been postulated as a potential cause of
certain psychiatric disorders that involve social behavioral deficits. In
particular, there is growing interest in intranasal OT as a potential treatment
for certain psychiatric disorders, and preliminary pre-clinical and clinical
studies suggest efficacy in alleviating some of the associated symptoms. However,
the vast majority of research participants in these studies have been male, and
there is evidence for sexually differentiated effects of nonapeptides in both
humans and non-human animals. To date, no study has investigated the effect of
intranasal OT on brain function in human males and females within the same
paradigm. Previously, in a randomized, placebo-controlled, double-blind fMRI
study, we reported effects of intranasal OT and AVP on behavior and brain
activity of human males as they played an interactive social game known as the
Prisoner's Dilemma Game. Here, we present findings from an identical study in
human females, and compare these with our findings from males. Overall, we find
that both behavioral and neural responses to intranasal OT and AVP are highly
sexually differentiated. In women, AVP increased conciliatory behavior, and both
OT and AVP caused women to treat computer partners more like humans. In men, AVP
increased reciprocation of cooperation from both human and computer partners.
However, no specific drug effects on behavior were shared between men and women.
During cooperative interactions, both OT and AVP increased brain activity in men
within areas rich in OT and AVP receptors and in areas playing a key role in
reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain,
insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in
some cases actually decreased brain activity in these regions in women. OT
treatment rendered neural responses of males more similar to responses of females
in the placebo group and vice versa, raising the prospect of an inverted u-shaped
dose response to central OT levels. These findings emphasize the need to fully
characterize the effects of intranasal OT and AVP in both males and females and
at multiple doses before widespread clinical application will be warranted.
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