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Introduction Unraveling the intrinsic links among sex, emotion, and reproduction relies on a focused exploration of putative factors. Identifying a factor that unites these fundamental components of human behavior has [...], BACKGROUND. Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. METHODS. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. RESULTS. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin's enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. CONCLUSIONS. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. FUNDING. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).

The nucleus accumbens is a brain region in which limbic and motor inputs converge. How these information modalities shape accumbens output is not clearly understood. Here, we report that synaptic inputs from the prefrontal cortex and limbic structures interact differently depending on their timing. Coincident inputs may result in enhancing information flow through the nucleus accumbens. Responses to asynchronous inputs are affected by their relative order of arrival, with limbic inputs allowing subsequent prefrontal responses, and prefrontal inputs dampening limbic responses. These mechanisms allow for both coincidence detection and input selection in this integrative brain region.