Associative learning switches DEET valence from aversive to appetitive in Aedes aegypti

ABSTRACT Repellents are central to personal protection and to reducing transmission of mosquito-borne diseases. Although substantial effort has been devoted to identifying the sensory and molecular pathways underlying repellent detection, the diversity of reported modes of action has hindered the development of a unified framework. It is generally assumed that insects respond to repellents in a fixed, aversive manner. However, an unexplored possibility is how plastic the innate meaning of repellents may be. We present experiments testing whether the innate response of Aedes aegypti to DEET (the gold-standard repellent) can be shifted from aversion to attraction. First, we identified and validated an appetitive behavioural response in mosquitoes equivalent to PER conditioning in flies and bees: the biting attempt response (BAR). Next, we trained individual mosquitoes to associate DEET with a blood meal using Pavlovian conditioning. We then examined whether mosquitoes trained with blood as a positive reinforcer would display the BAR when presented with DEET alone or on host skin. Finally, we trained females to associate DEET with sugar and tested their subsequent response to DEET alone. Across all experiments, trained mosquitoes showed a reversal in the valence of DEET, shifting from innate avoidance to a learned appetitive response. These results demonstrate that experience can render DEET attractive by establishing associations with two rewarding contexts: vertebrate blood feeding and plant sugar feeding. We discuss the implications of this learned attraction for understanding repellent mechanisms and for designing strategies to improve personal protection.