Abstract
E-cigarettes also known as vape, are rapidly gaining recognition as having potential neurological consequences, yet their neural effects on sensory valence and associative learning remain poorly understood, necessitating urgent investigation into their potential neurocognitive effects. This is particularly important because nicotine, the primary psychoactive component in most vape liquid, acts directly on nicotinic acetylcholine receptors (nAChRs) in the brain. Hence, the role of nAChRs in the control of neural learning and memory in response to this drug is fundamental. Here, we investigated how vape exposure modulates olfactory behaviour, reinforcement processing, and the influence α7 or β2 nicotinic acetylcholine receptors (nAChR) mutation in Drosophila melanogaster. In this study, vape exposure significantly affected motor performance and cholinergic function, as evidenced by altered negative geotaxis and acetylcholinesterase (AChE) activity after chronic treatment with 0.06, 0.08, and 0.12 mg/mL vape in different flies genotypes. Addionally, using a combination of innate odour preference and conditioning assays, we found that wild-type flies displayed an inherent attraction to strawberry odour and avoidance of aversive one (marula). However, exposure to vape altered these intrinsic preferences, reversing attraction to aversion and attenuating innate avoidance exhibited as "addiction-like" behaviour in wild-type flies. Notably, these vape-induced shifts in odour valence were abolished in nAChRα7[-/-] and nAChRβ2[-/-] mutants, implicating nicotinic acetylcholine receptor signaling in mediating nicotine's neuromodulatory effects. However, α7 and β2 significantly differ in odour discrimination and detection of chemically related odour pairs, while β2 nAChR mutants display a strong resistance to learning, further impairing memory performance. Together, our findings indicate that vape acts not merely as an associative cue but as a neuromodulator that reshapes innate sensory valence through α7 and β2-containing nAChRs. This work establishes Drosophila as a powerful genetic model for understanding the neural mechanisms by which vape exposure alters odour valence and reinforcement processing, providing new insight into the addictive properties of vaping.
