Failure to mate enhances investment in behaviors that may promote mating reward and impairs the ability to cope with stressors via a subpopulation of Neuropeptide F receptor neurons

Living in dynamic environments such as the social domain, where
interaction with others determines the reproductive success of
individuals, requires the ability to recognize opportunities to obtain
natural rewards and cope with challenges that are associated with
achieving them. As such, actions that promote survival and reproduction
are reinforced by the brain reward system, whereas coping with the
challenges associated with obtaining these rewards is mediated by
stress-response pathways, the activation of which can impair health and
shorten lifespan. While much research has been devoted to understanding
mechanisms underlying the way by which natural rewards are processed by
the reward system, less attention has been given to the consequences of
failure to obtain a desirable reward. As a model system to study the
impact of failure to obtain a natural reward, we used the well-established
courtship suppression paradigm in Drosophila melanogaster as means to
induce repeated failures to obtain sexual reward in male flies. We
discovered that beyond the known reduction in courtship actions caused by
interaction with non-receptive females, repeated failures to mate induce a
stress response characterized by persistent motivation to obtain the
sexual reward, reduced male-male social interaction, and enhanced
aggression. This frustrative-like state caused by the conflict between
high motivation to obtain sexual reward and the inability to fulfill their
mating drive impairs the capacity of rejected males to tolerate stressors
such as starvation and oxidative stress. We further show that sensitivity
to starvation and enhanced social arousal is mediated by the disinhibition
of a small population of neurons that express receptors for the fly
homologue of neuropeptide Y. Our findings demonstrate for the first time
the existence of social stress in flies and offers a framework to study
mechanisms underlying the crosstalk between reward, stress, and
reproduction in a simple nervous system that is highly amenable to genetic
manipulation.