The neuropeptide drosulfakinin enhances choosiness and protects males from the aging effects of social perception.

The motivation to reproduce is a potent natural drive, and the social behaviors that induce it can severely impact animal health and lifespan. Indeed, in males, accelerated aging associated with reproduction arises not from the physical act of courtship or copulation but instead from the motivational drive to court and mate. To better understand the mechanisms underlying social effects on aging, we studied male choosiness for mates. We found that increased activity of insulin-producing cells (IPCs) of the fly brain potentiated choosiness without consistently affecting courtship activity. Surprisingly, this effect was not caused by insulins themselves, but instead by drosulfakinin (DSK), another neuropeptide produced in a subset of the IPCs, acting through one of the two DSK receptors, CCKLR-17D1. Activation of IPC neurons also decreased food consumption, while activation of neurons outside of IPCs affected neither choosiness nor feeding, suggesting an overlap between neurons modulating choosiness and those influencing satiety. Broader activation of neurons (both within and outside of the IPCs) was required to rescue the detrimental effect of female pheromone exposure on male lifespan, as was the function of both DSK receptors. The same broad set of neurons was found to reinforce normally aversive feeding interactions, but only after exposure to female pheromones, suggesting that perception of the opposite sex gates rewarding properties of these neurons. We speculate that broad neuron activation is associated with states of satiety and social experience, which under stressful conditions is rewarding and beneficial for lifespan.