Flies get anxious too. Or at least they experience something that manifests in similar behavior and can be alleviated by the same drugs that soothe us. The discovery could speed up the quest for better anti-anxiety treatments.
Vast research effort goes into the pharmacological treatment of mood disorders, but sufferers of moderate or severe anxiety have seen little progress for decades. That is despite the fact that anxiety disorders are considered the most common mental illness in the United States.
"Anxiety research in rodents has been frustrated by the small sample sizes typically used in experiments and the complexity of the mammalian brain," Dr. Adam Claridge-Chang of Duke-NUS Medical School in Singapore said in a statement. "Many scientists in the rodent anxiety field would agree that this drug development failure does not imply a 'failure to translate,' but rather an inadequate understanding of the basic neurogenetic mechanisms of anxiety.”
What is needed, then, is a simpler model – an animal that experiences anxiety but has a less complex, and therefore easier to study, brain, preferably one that is also well understood and cheap to work with. Dr. Farhan Mohammad wondered if Drosophila fruit flies, a favorite model for geneticists, might be the answer. He noticed that in an enclosed chamber, flies will often follow the walls, and pointed to similar behavior in rodents.
“Wall-following behavior in rodents has long been linked to anxiety, so I hypothesized that fly wall-following was also related to anxiety," Mohammad said. The link may seem tenuous, but Mohammad followed it up by giving flies diazepam (Valium). Just as with rats, the anti-anxiety medication led to the flies spending more time in the middle of the room. On the other hand, inducing more stressful situations made the flies stick more closely to the walls.
In Current Biology, Mohammad and Claridge-Chang report on these observations and their attempts to alter the symptoms of anxiety by manipulating the d5-HT1A, d5-HT1B and dSerT genes. These are similar to genes that influence serotonin release and uptake in mammals, and whose deletion or over-expression in mice changes anxious behavior.
Changes to d5-HT1A expression produced only minor effects, but d5-HT1B and dSerT proved to have an influence on the flies' wall-following behavior. “The effects of these interventions were strikingly concordant with rodent anxiety, verifying that these behaviors report on an anxiety-like state,” the authors noted.
By fiddling with the genetics of the simple insect brain, Mohammad and Claridge-Chang identified five genes whose association with anxiety had not been observed before. Despite as much as 700 million years of evolutionary separation between humans and fruit flies, similar genes exist in mammals. The researchers believe these genes justify further research, potentially providing targets for drugs that may provide relief for sufferers of anxiety disorders.
The discovery that fruit flies show behavior indicative of an emotion previously only attributed to vertebrates could raise unwelcome questions for medical research ethics panels, however.