Transient neuromodulation can have long-lasting effects on neural circuits and motivational states^1,2,3,4. Here we examine the dopaminergic mechanisms that underlie mating drive and its persistence in male mice. Brief investigation of females primes a male’s interest to mate for tens of minutes, whereas a single successful mating triggers satiety that gradually recovers over days⁵. We found that both processes are controlled by specialized anteroventral and preoptic periventricular (AVPV/PVpo) dopamine neurons in the hypothalamus. During the investigation of females, dopamine is transiently released in the medial preoptic area (MPOA)—an area that is critical for mating behaviours. Optogenetic stimulation of AVPV/PVpo dopamine axons in the MPOA recapitulates the priming effect of exposure to a female. Using optical and molecular methods for tracking and manipulating intracellular signalling, we show that this priming effect emerges from the accumulation of mating-related dopamine signals in the MPOA through the accrual of cyclic adenosine monophosphate levels and protein kinase A activity. Dopamine transients in the MPOA are abolished after a successful mating, which is likely to ensure abstinence. Consistent with this idea, the inhibition of AVPV/PVpo dopamine neurons selectively demotivates mating, whereas stimulating these neurons restores the motivation to mate after sexual satiety. We therefore conclude that the accumulation or suppression of signals from specialized dopamine neurons regulates mating behaviours across minutes and days.

^{瞬态神经调节可以对神经回路和动机状态1,2,3,4}产生持久的影响。在这里，我们研究了作为交配驱动基础的多巴胺能机制及其在雄性小鼠中的持久性。对雌性的简短调查会激发雄性在数十分钟内交配的兴趣，而一次成功的交配会引发饱腹感，并在^{第 5天逐渐恢复}. 我们发现这两个过程都由下丘脑中专门的前腹侧和视前脑室周围 (AVPV/PVpo) 多巴胺神经元控制。在对雌性进行调查期间，多巴胺在内侧视前区 (MPOA) 中短暂释放，该区域对交配行为至关重要。MPOA 中 AVPV/PVpo 多巴胺轴突的光遗传学刺激概括了暴露于女性的启动效应。使用光学和分子方法来跟踪和操纵细胞内信号传导，我们表明这种启动效应来自 MPOA 中交配相关多巴胺信号的积累，通过环磷酸腺苷水平和蛋白激酶 A 活性的积累。MPOA 中的多巴胺瞬变在成功交配后被废除，这很可能确保禁欲。符合这个想法，抑制 AVPV/PVpo 多巴胺神经元选择性地抑制交配，而刺激这些神经元可恢复性饱腹后交配的动力。因此，我们得出结论，来自特化多巴胺神经元的信号的积累或抑制调节了数分钟和数天的交配行为。