Whether you're a human, a mouse, or even a fruitfly, losing sleep is a bad thing, leading to physiological effects and behavioral changes. One example that has been studied for many years is a link between sleep loss and aggression. But it can be difficult to distinguish sleep loss effects from stress responses, especially in rodent or human models.

A team of researchers from the Perelman School of Medicine at the University of Pennsylvania used fruitflies to probe deeper into the cellular and molecular mechanisms that govern aggression and sleep. They found that sleep deprivation reduces aggression in fruitflies and affects their reproductive fitness. The team also identified a related molecular pathway that might govern recovery of normal aggressive behaviors.  The work was published in eLife this week.

First author Matthew Kayser, MD, PhD, an assistant professor of Psychiatry, and the team focused on several chemicals that have been associated with aggression in fruitflies and other species. “There has been a lot of work on these monoamines, the same ones that are potentially involved in some aspects of mammalian aggression," explained Kayser. “We asked what happens if we try to activate dopamine receptors or octopamine [the insect version of norepinephrine in mammals], a type of monoamine, after sleep loss in flies." 

After flies were given the chlordimeform (CDM), an octopamine agonist – a molecule that initiates a physiological response when binding to a cell-surface receptor -- and the dopamine agonist L-DOPA and then sleep deprived, the researchers saw that CDM rescued aggressive behavior, but L-DOPA did not. “If you activate octopamine receptors, you rescue the fighting behavior," said Kayser. “The other drug L-DOPA makes them really active, but they're not fighting.” Neither drug affected fighting behaviors when flies were not sleep deprived.

Kayser notes that the relative simplicity of the fruitfly model compared to working with mammals is a more direct approach to studying the sleep-aggression link. “We first sleep deprived the flies and looked at their fighting behavior, and saw a huge, very clear effect on behavior," he said. “Suddenly they go from fighting quite a bit to sharing resources and not fighting much.”

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