Biphasic Neurostimulatory Effects of Caffeine on Dopamine-Mediated Locomotor Circuits in Drosophila melanogaster

Abstract

This study aimed to examine how caffeine affects the movement of Drosophila melanogaster in a dose-dependent manner. It also aimed to evaluate the use of Drosophila as an ethical and inexpensive model for studying the neurobehavioral effects of stimulants, which are relevant to human health.

Experimental groups were given freshly prepared caffeine solutions from instant coffee (a stock solution of about 3.5 mg/mL). These solutions were diluted to concentrations of 50% (1.75 mg/mL), 75% (2.63 mg/mL), and 100% (3.50 mg/mL). A control group was not treated. Locomotor activity was measured using the negative geotaxis assay over six hours. The average climbing height (in centimeters) and percent of active flies were recorded for each group.

The 75% group demonstrated peak locomotor performance (mean climbing height: 10.1 ± 0.7 cm; 9/10 flies active), significantly exceeding the control (6.2 ± 0.5 cm; 5/10 active) and confirming caffeine's stimulatory effect at moderate doses. The 100% concentration produced a decline in activity (7.5 ± 0.8 cm; 6/10 active) relative to the 75% group, indicating physiological stress and impaired neuromuscular coordination at excessive doses, consistent with a concentration-dependent biphasic response.

This study provides direct quantitative evidence of a biphasic locomotor response across a graded, ecologically relevant caffeine concentration series in wild-type Drosophila under standardised laboratory conditions, establishing that neural stimulation occurs only within an optimal physiological range. The results underscore the utility of Drosophila melanogaster as a reproducible, and accessible model for neuropharmacological investigation and highlight the public health relevance of dosage regulation among young caffeine consumers.