Han, K.-A. | Search bioRxiv

bioRxiv2025

Nighttime Caffeine Intake Increases Motor Impulsivity

Caffeine is commonly consumed at night by shift workers and military personnel for its wake-promoting effect, yet its adverse effects on behavior remain underexplored. Here, we show that nighttime caffeine intake impairs inhibitory control in Drosophila melanogaster, resulting in impulsive motor behavior, with females more sensitive than males. This effect is independent of hyperactivity or sleep loss, as walking speed was unchanged, and artificial sleep deprivation via light or mechanical stimulation did not elicit similar deficits. Notably, daytime caffeine feeding did not impair inhibitory control, highlighting a circadian gating of caffeines behavioral impact. Mechanistically, we identify dopamine signaling as a key mediator of caffeine-induced impulsivity. Reduced dopamine synthesis (pale/+), silencing of PAM dopaminergic neurons, or altered dopamine transporter activity (fumin/+) attenuated or exacerbated caffeine-induced impulsivity. Targeted manipulations identified the dopamine D1 receptor (dDA1/Dop1R1) in the mushroom body (MB) /{beta} and {gamma} lobes as essential for this effect, with {gamma}-lobe neurons exhibiting heightened sensitivity. These findings reveal a circadian- and dopamine-dependent mechanism through which nighttime caffeine impairs behavioral inhibition.

animal behavior and cognition↗

bioRxiv2025

Social context and dopamine signaling converge in the mushroom body to drive impulsivity

Organisms adapt their behaviors flexibly in response to various internal and environmental factors. However, how and where these factors converge in the brain to alter behavior is not well understood. In this study, we examine how social context interacts with dopamine activity to influence inhibitory control in Drosophila. We found that, regardless of social context--whether isolated or in groups--wild-type flies consistently showed strong movement suppression in a go/no-go task that measures action restraint. In contrast, flies with enhanced dopamine activity suppressed their movements when tested alone or with potential mates but exhibited impulsive behaviors when exposed to same-sex peers. This social-context-dependent impulsivity was shown to rely on dopamine-D1 receptor-cAMP signaling in mushroom body (MB) neurons. Remarkably, activating the MB was sufficient to induce impulsivity, even without dopamine input or a social context. Our findings highlight MB as a critical hub where social context and dopamine signaling converge to regulate impulsive behavior in Drosophila. Signficance statementThis study demonstrates that impulsivity results from the interplay between elevated dopamine levels and social context, rather than dopamine alone, with the mushroom body (MB) serving as a key neural hub for integrating these signals in Drosophila. Social stimuli, such as the presence of same-sex peers, disrupt inhibitory control in a context-dependent manner, highlighting the importance of multimodal sensory inputs and MB activity. These findings challenge the isolation-focused approach in traditional impulsivity research and underscore the need to account for social influences when investigating cognitive processes and disorders like ADHD, autism, and substance use, where social settings often amplify symptoms. ClassificationGenetics / Neuroscience

animal behavior and cognition↗