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The preputial glands of house mice express the gene for the fifth melanocortin receptor (MC5-R) and are a primary source of urinary pheromones involved in inter-male aggression. A 'resident-intruder' behavioral model was used to compare the responses of resident males to urine from mice with an engineered disruption of the fifth melanocortin receptor (MC5-RKO) with residents' responses to urine from wild-type mice (WT). Each type of urine was presented in combination with a castrated intruder male to provide the appropriate biological context. Resident males responded with a longer latency to bite when the urine was from gonadally intact WT males compared with urine from MC5-RKO mice. These results are consistent with the hypothesis that activation of the fifth melanocortin receptor in the preputial glands of male house mice causes excretion of urinary pheromones that delay aggressive responses by other males.

Several short-duration tests have demonstrated that the surgical removal of the vomeronasal organ (VNX) from sexually-inexperienced male rodents results in a reduction in copulatory behavior, compared to the effects of sham surgery (SHAM). We extended these studies to adult male prairie voles, Microtus ochrogaster, and substantially increased the duration of the tests. During the initial interactions with females, VNX males spent significantly less time with their noses in close proximity to the females than did SHAM males. Moreover, only two of nine VNX males sired offspring after having been paired with females for 8 weeks, whereas nine of 12 SHAM males sired offspring in that interval. We also found that VNX and SHAM males were equivalently non-aggressive to an anesthetized stimulus-male prior to being paired with females. However, after spending 2 weeks paired with a female, the VNX males were significantly less aggressive than were the SHAM males, possibly as a result of having copulated less often. In a later test, nearly all of the VNX and SHAM males that sired offspring were vigorously aggressive to a stimulus male. We conclude that the stimulation of the vomeronasal system in sexually-inexperienced male prairie voles is important for maximal reproductive performance and that the VNX-induced impairment in reproduction is associated with a decrease in inter-male aggression. The possible sensory effects of the vomeronasal system on the neural and endocrine control of reproduction and behavior are discussed.