The irritant receptor TRPA1 mediates the mosquito repellent effect of catnip

Catnip (Nepeta cataria) is a common garden herb well known for its euphoric and hallucinogenic effects on domestic cats,^1–3 for its medicinal properties,^4,5 as well as for its powerful repellent action on insects.^6,7 Catnip extracts have been proposed as a natural alternative to synthetic insect repellents, such as N,N-diethyl-3-methylbenzamide (DEET),^8,9 but how catnip triggers aversion in insects is not known. Here, we show that, both in Drosophila melanogaster flies and Aedes aegypti mosquitoes, the major mediator of catnip repellency is the widely conserved chemical irritant receptor TRPA1. In vitro, both catnip extract and its active ingredient nepetalactone can directly activate fly and mosquito TRPA1. In vivo, D. melanogaster and Ae. aegypti TRPA1 mutants are no longer repelled by catnip and nepetalactone. Interestingly, our data show that some, but not all, fly and mosquito TRPA1 variants are catnip targets. Moreover, unlike the broad TRPA1 agonist allyl isothiocyanate (AITC) (an active ingredient of tear gas and wasabi), catnip does not activate human TRPA1. Our results support the use of catnip and nepetalactone as insect-selective irritants and suggest that, despite TRPA1’s broad conservation, insect TRPA1 can be targeted for the development of safe repellents. Catnip has been used for millennia as an insect repellent. Melo et al. find that catnip and its major iridoid component nepetalactone activate insect isoforms of the irritant receptor TRPA1. Mosquitoes lacking TRPA1 are no longer repelled by catnip. Catnip does not activate human TRPA1, and this supports its use as a safe natural mosquito repellent.