Lesions of orexin neurons block conditioned place preference for sexual behavior in male rats

► Orexin neurons in the lateral hypothalamic area and perifornical-dorsomedial hypothalamus are activated by cues predictive of sexual reward. ► Cell body specific lesions of orexin neurons block mating-induced conditioned place preference, but do not block conditioned place aversion to lithium chloride induced visceral illness or sexual performance. ► These findings suggest that orexin is critical for reward processing and specifically for conditioned cue induced seeking of sexual reward.