The pharmacological and functional characterization of the serotonergic system in Anopheles gambiae and Aedes aegypti: influences on flight and blood-feeding behavior.

ABSTRACT

Aedes aegypti and Anopheles gambiae harbor the causative agents of diseases such as dengue fever and malaria, afflicting human morbidity and mortality worldwide. Given the worldwide emergence of resistance to insecticides, the current mainstay for vector control, identification of alternative modes of action for future insecticides is paramount. The serotonergic (5-HT) system has been documented to impact physiological mechanisms involved in disease transmission, suggesting its potential as a new mode of action target for future insecticide development. Target 5-HT receptors were cloned and expressed in the HEK293 cell line for functional and pharmacological characterization. Manipulation of the 5-HT system through microinjection of compounds suggests its involvement in the modulation of flight performance and blood-feeding behavior. By attenuating these two determinants of vectorial capacity, transmission and burden of disease could effectively be reduced. Considering these positive global health implications, the 5-HT system is a compelling target for the novel insecticide pipeline.