Oxytocin can increase or decrease anxiety-related behaviors.

Duque-Wilckens et al. report experiments in mice showing that oxytocin, usually regarding as reducing anxious behaviors, enables stress-induced social anxiety behaviors if it is produced outside of its normal source in the hypothalmus.  

Significance

The neuropeptide oxytocin is an important regulator of social behavior and is widely considered to reduce anxiety-related behaviors. However, growing evidence suggests that sometimes oxytocin increases anxiety. How can the same molecule have such different effects on behavior? Here we provide evidence that oxytocin produced outside of the hypothalamus is necessary and sufficient for stress-induced social anxiety behaviors. This suggests that the diverse effects of oxytocin on anxiety-related behaviors are mediated by circuit-specific oxytocin action.

Abstract

Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knockdown prevented social stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors, including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naïve mice increased social vigilance and reduced social approach. These results show that a population of extrahypothalamic oxytocin neurons plays a key role in controlling stress-induced social anxiety behaviors.