Editors' ChoiceNeuroscience

Serotonin Gives Oxytocin a Helping Hand

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Science Translational Medicine  16 Oct 2013:
Vol. 5, Issue 207, pp. 207ec172
DOI: 10.1126/scitranslmed.3007759

The neuropeptide oxytocin has been implicated in social behavior and is being evaluated as a possible treatment for autism spectrum disorders and schizophrenia, but the neural mechanisms through which oxytocin modulates social behavior remain largely unknown. One possibility is that social interaction recruits the brain’s reward circuits and that oxytocin plays a role in this process, which ultimately reinforces social behavior. In a recent study, Dolen et al. elucidate key circuits and mechanisms through which oxytocin can modulate social behavior via actions on the nucleus accumbems, a key component of the brain’s reward circuitry.

Dolen et al. studied social conditioned place preference (social CPP), in which mice prefer to spend time in a chamber that was previously associated with social interaction instead of in a chamber previously associated with social isolation. This task measures the rewarding effects of social interactions. Dolen et al. found that ablating presynaptic oxytocin receptors specifically on projections from the dorsal raphe nucleus to the nucleus accumbens is sufficient to eliminate this preference. They carried out additional experiments suggesting that oxytocin acts by increasing serotonin release from dorsal raphe projections to the nucleus accumbens and that serotonin acts on 5-HT1B receptors in the nucleus accumbens to cause long-term depression of excitatory synapses. Indeed, they found that activating 5-HT1B receptors in the nucleus accumbens is itself sufficient to impair social CPP. Intriguingly, 5-HT1B receptors have previously been implicated in social behaviors and autism.

These studies pinpoint a specific synapse on which oxytocin can act to modulate social behavior in mice and suggest that serotonin mediates key actions of oxytocin on reward circuits. Now that this system has been uncovered, future studies should explore both its inputs, by elucidating how oxytocin release in the nucleus accumbens is regulated, and its outputs, by studying how long-term depression of specific excitatory synapses alters the flow of information into the nucleus accumbens. Working out exactly how oxytocin elicits serotonin release and long-term depression may also reveal specific molecular mechanisms that are dysfunctional in autism and related conditions.

G. Dolen et al., Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 501, 179–184 (2013). [Asbtract]

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