Kisspeptin participates in the positive reward state induced by paced mating and modulates sexual receptivity and paced mating behavior in female rats.

Kisspeptin (Kp), a potent regulator of the hypothalamic-pituitary-gonad axis, was recently shown to be involved in partner preference and sexual receptivity in females. Interestingly, Kp and its receptor (Kiss1r) are expressed in brain regions involved in the reward and motivation of reinforcing behaviors. Therefore, in the present study, we designed 3 experiments to determine the participation of Kp in female sexual behavior and the positive affective (PA) reward state induced by paced mating (PM). In all experiments, we used sexually naïve ovariectomized Wistar female rats primed with estradiol benzoate (EB, 2.5 μg/rat) 48 h before behavioral tests. In experiment 1 (n = 9), we tested the effect of Kp on PM. We demonstrated that Kp-10 (14 nmol) induced similar levels of receptivity to treatment with EB + progesterone and facilitated PM by reducing the return latency after intromissions. In experiment 2 (n = 8), we evaluated the effect of p234 penetratin, a Kiss1r antagonist, on PM. The administration of p234 in doses of 7.5 nmol and 15 nmol reduced the mean lordosis intensity and increased mount and intromission return latencies. Finally, in Experiment 3, we tested the capacity of Kp to induce a PA state or the antagonist to block the reward state induced by PM. Kp-10 (7 and 14 nmol) induced a clear conditioned place preference. This reward state and that produced by PM were blocked by p234 (15 nmol). Our findings underscore the critical role of Kp in modulating female sexual behavior and the PA state associated with PM, highlighting its potential to enhance sexual motivation.