Immediately after birth, female

rabbits use a mammary pheromone, 2-methylbut-2-enal (2MB2), to promote suckling in their young. The response is so robust that newborn rabbits with no prior experience of the pheromone Bortezomib will display stereotypical search and grasping behaviours to a glass rod dipped in 2MB2 [25]. When pheromone is paired with a neutral odour, the rabbit pups display the behaviour on subsequent exposure to the odour [26]. This demonstrated that mammalian pheromones can condition previously neutral odours with bioactivity if an animal perceives them concurrently. This mechanism is ideal for mammary pheromones, as it is clearly advantageous to a rabbit pup to seek milk on the detection of almost

any maternal odour. However, in less controlled environments it risks a behaviour being inappropriately released due to accidental associations between the pheromone and a non-relevant odour. Roberts and colleagues tested whether a male-mouse specific sex-pheromone Veliparib could also mediate olfactory learning [27]. The pheromone (a non-volatile major urinary protein called MUP20 or, alternatively, darcin) was innately attractive to female mice, but the volatile fraction of male urine was not. However, after experiencing the volatile fraction with MUP20, females subsequently became attracted to the volatiles alone [27]. Interestingly, MUPs directly bind, with high affinity, a number of small volatile chemicals that are specific

Ergoloid to male urine [28]. In a natural setting it may be advantageous for female mice to learn volatiles associated with MUP20, as these can be detected over greater distances than a non-volatile protein. The same authors have since reported that MUP20 can also induce spatial learning [29••]. Remarkably, after a single contact with a recombinant MUP20, females repeatedly returned to the same location for up to fourteen days. Thus pheromone-mediated learning is not limited to olfactory conditioning, but is probably multisensory. Most recently an even more complex example of pheromone-mediated learning has been described [18••]. MUPs are encoded by a multi-gene family in mice and each adult male stably expresses large amounts of between four and twelve proteins in his urine 4 and 30]. Intriguingly, different males express different MUP combinations: only MUP20 is present in (almost) all males [27]. If MUP20 attracts females, what function might variably expressed paralogues serve? Using a series of subtractive and additive experiments, Kaur et al. found that dominant male mice learned their endogenous MUP code to distinguish themselves from others [18••].