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Associative learning turns DEET from aversive to appetitive in Aedes aegypti

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Associative learning switches DEET valence from aversive to appetitive in Aedes aegypti | Journal of Experimental Biology | The Company of Biologists

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Volume 229, Issue 10

May 2026

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RESEARCH ARTICLE|
28 May 2026


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

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Claudio R. Lazzari

0000-0003-3703-0302

,

Claudio R. Lazzari

Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing

1Institut de Recherche sur la Biologie de l'Insecte, UMR CNRS 7261 – University of Tours, 37200 Tours, France

Author for correspondence ([email protected])

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David De Luca,

David De Luca

Data curation, Investigation, Methodology, Validation, Writing – review & editing

1Institut de Recherche sur la Biologie de l'Insecte, UMR CNRS 7261 – University of Tours, 37200 Tours, France

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Ayelén Nally

0009-0003-2130-787X

,

Ayelén Nally

Data curation, Investigation, Methodology, Validation, Writing – review & editing

1Institut de Recherche sur la Biologie de l'Insecte, UMR CNRS 7261 – University of Tours, 37200 Tours, France2Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, University of Buenos Aires, C1428EGA Buenos Aires, Argentina

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Charly Dufour,

Charly Dufour

Data curation, Investigation, Methodology, Validation, Writing – review & editing

1Institut de Recherche sur la Biologie de l'Insecte, UMR CNRS 7261 – University of Tours, 37200 Tours, France

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Clément Vinauger

0000-0002-3704-5427

Clément Vinauger

Conceptualization, Validation, Writing – original draft, Writing – review & editing

3Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA

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Author and article information

Claudio R. Lazzari

https://orcid.org/0000-0003-3703-0302

Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing

1Institut de Recherche sur la Biologie de l'Insecte, UMR CNRS 7261 – University of Tours, 37200 Tours, France

David De Luca

Data curation, Investigation, Methodology, Validation, Writing – review & editing

1Institut de Recherche sur la Biologie de l'Insecte, UMR CNRS 7261 – University of Tours, 37200 Tours, France

Ayelén Nally

https://orcid.org/0009-0003-2130-787X

Data curation, Investigation, Methodology, Validation, Writing – review & editing

1Institut de Recherche sur la Biologie de l'Insecte, UMR CNRS 7261 – University of Tours, 37200 Tours, France2Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, University of Buenos Aires, C1428EGA Buenos Aires, Argentina

Charly Dufour

Data curation, Investigation, Methodology, Validation, Writing – review & editing

1Institut de Recherche sur la Biologie de l'Insecte, UMR CNRS 7261 – University of Tours, 37200 Tours, France

Clément Vinauger

https://orcid.org/0000-0002-3704-5427

Conceptualization, Validation, Writing – original draft, Writing – review & editing

3Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA

Author for correspondence ([email protected])

Competing interestsThe authors declare no competing or financial interests.

Received:
18 Nov 2025

Accepted:
13 Apr 2026

Online ISSN: 1477-9145
Print ISSN: 0022-0949

Funding

Funding Group: Award Group: Funder(s):  The Journal of Experimental Biology

Funding Group: Award Group: Funder(s):  University of Tours

Funding Group: Award Group: Funder(s):  Centre national de la recherche scientifique

© 2026. Published by The Company of Biologists2026https://www.biologists.com/user-licence-1-2/

J Exp Biol (2026) 229 (10): jeb251935.

https://doi.org/10.1242/jeb.251935

Article history

Received:
18 Nov 2025

Accepted:
13 Apr 2026

Related content

This is a related article to:
ECR Spotlight – Ayelén Nally

This is a related article to:
DEET insect repellent at risk: mosquitoes can learn it means dinner

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Citation
Claudio R. Lazzari, David De Luca, Ayelén Nally, Charly Dufour, Clément Vinauger; Associative learning switches DEET valence from aversive to appetitive in Aedes aegypti. J Exp Biol 15 May 2026; 229 (10): jeb251935. doi: https://doi.org/10.1242/jeb.251935
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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.

Keywords:
Mosquitoes,
Repellents,
Olfactory conditioning,
Disease vectors,
Personal protection

Footnotes

Author contributionsConceptualization: C.R.L., C.V.; Data curation: C.R.L., D.D.L., A.N., C.D.; Formal analysis: C.R.L.; Funding acquisition: C.R.L.; Investigation: C.R.L., D.D.L., A.N., C.D.; Methodology: C.R.L., D.D.L., A.N., C.D.; Project administration: C.R.L.; Resources: C.R.L.; Supervision: C.R.L.; Validation: C.R.L., D.D.L., A.N., C.D., C.V.; Visualization: C.R.L.; Writing – original draft: C.R.L., C.V.; Writing – review & editing: C.R.L., D.D.L., A.N., C.D., C.V.

FundingA.N. was supported by a Travelling Fellowship from The Journal of Experimental Biology. This study was supported by recurrent funds from the University of Tours, the ECOS-Sud programme ‘Understanding Repellence’, and the IRP-INNE programme from Centre national de la recherche scientifique (CNRS) REPEL.

Data and resource availabilityDatasets are available in Mendeley at doi:10.17632/66cfdwtcs8.1. All other relevant data and details of resources can be found within the article and its supplementary information.

ECR SpotlightThis paper has an associated ECR Spotlight interview with Ayelén Nally.

© 2026. Published by The Company of Biologists2026https://www.biologists.com/user-licence-1-2/

Keywords:
Mosquitoes,
Repellents,
Olfactory conditioning,
Disease vectors,
Personal protection

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The study investigated whether the innate aversion of *Aedes aegypti* mosquitoes to DEET, a standard repellent, could be reversed through associative learning, shifting this valence from aversive to appetitive. The researchers aimed to explore the possibility that the innate meaning of repellents is plastic, rather than fixed.

To achieve this, the study first identified and validated an appetitive behavioral response in mosquitoes equivalent to the biting attempt response (BAR) observed in flies and bees, which served as the measurable outcome. Subsequently, the researchers employed Pavlovian conditioning techniques to train individual mosquitoes to associate DEET with rewarding stimuli. Specifically, they trained mosquitoes to associate DEET with a blood meal, which served as a positive reinforcer. They then examined whether these trained mosquitoes exhibited the BAR when presented with DEET alone or when DEET was applied to host skin. Furthermore, the study explored a second associative link by training female mosquitoes to associate DEET with sugar, assessing their subsequent behavioral response to DEET when presented in isolation.

The results demonstrated that across all experimental manipulations, the trained mosquitoes exhibited a reversal in the valence of DEET, transitioning from their innate avoidance behavior to a learned appetitive response. This shift was mediated by the establishment of associations between DEET and two rewarding contexts: vertebrate blood feeding and plant sugar feeding. These findings suggest that experience plays a role in modifying the perception of repellents, indicating that learned associations with rewarding contexts can render chemical substances attractive to organisms. The authors discuss the implications of this learned attraction for a deeper understanding of the mechanisms underlying repellent action and for developing more effective strategies for personal protection.