Genetic variation contributes to heterogeneity in the prevalence of complex disorders such as addiction. The genetic risk for developing a substance use disorder can vary between drugs. The estimated heritability rate of cocaine addiction is 72%, higher than any other drug. Despite recognition of this significant genetic component, little is known about the specific genes and mechanisms that lead to the development of cocaine addiction. Drosophila is an effective model organism for identifying the genes that underlie complex behaviors, including addiction. While Drosophila exposed to cocaine display features of intoxication similar to those observed in mammals, there is currently no model of cocaine self-administration in flies. Because cocaine is a natural insecticide, we wondered if Drosophila might naively avoid it through bitter chemosensory detection. To answer this question, we performed cocaine consumption and preference assays comparing wild-type flies and bitter-taste mutants. Our results demonstrate that Drosophila detect and avoid cocaine through bitter sensing gustatory neurons, and that this process requires gustatory receptor 66a (Gr66a). Additionally, we identify a peripheral mechanism of avoidance through cocaine detection with Drosophila legs. Our findings reveal that preingestive mechanisms of toxin detection play a significant role in Drosophila cocaine avoidance and provide evidence that disrupting gustatory perception of cocaine is essential to for self-administration and therefore, developing a model of self-administration in Drosophila.
Previous researchers have reported that aerobic exercise improves cognition in older adults; however, few researchers have examined the role of arousal on improvements in cognition after exercise. The purpose of this study was to understand how changes in arousal acutely affect changes in cognitive performance after a single session of light compared to moderate intensity aerobic exercise. Cognitively normal older adults (N = 34) were enrolled in a randomized controlled trial where they were asked to complete the N-back task with faces, a cognitive task used to test working memory, in an fMRI scanner. On separate days, the task was completed before and 15 to 20 minutes after light and moderate intensity exercise. An intervention was also completed, but our question focuses on the acute effects of exercise rather than training. Arousal was measured before and after exercise through a questionnaire and a direct measure of physiological activation of the sympathetic nervous system with galvanic skin response (GSR). On average, resting GSRs decreased from pre- to post-exercise scan; however, the change was not statistically significant. The decrease in arousal after light exercise indicated that older adults had decreased sympathetic activity after both light and moderate intensity exercise. By contrast, N-back task performance improved most after moderate compared to light intensity exercise. Together, evidence that sympathetic activity tended to decrease generally for both intensities, whereas cognitive improvements were more specific, suggests that changes in arousal at rest were not a critical factor connecting exercise and improved working memory in this study.
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