The “Tippling Point” – Dr. Galit Shohat-Ophir and the Secret of Barfly Success
Rejected by the girl of his dreams, the male of the species has been known to seek out an alcoholic consolation prize down at the bar. But even when the species in question is not human, and even when the “bar” is an ethanol-laced laboratory beaker, this sex-specific coping mechanism still holds true – providing a rare glimpse into how neural circuitry and behavior are both modified by social experience.
“There is more to the social life of the common fruit fly than meets the eye,” says Dr. Galit Shohat-Ophir, a lecturer in the Mina & Everard Goodman Faculty of Life Sciences who trained at the Weizmann Institute and completed post-doctoral fellowships at UCSF and the Howard Hughes Medical Institute in Virginia. “Males can differentiate between virgin females – who are receptive to their advances – and females that have already mated. Ethanol vapor causes flies to lose their inhibition, then their coordination; in other words, fruit flies, like mammals, can get rip-roaring drunk. In my post-doctoral research – which was published in Science – I explored the connection between sex and alcohol, and examined how sexual ‘success’ affects flies’ alcohol-seeking behavior.”
Shohat-Ophir explains that fruit flies’ neural mechanism for processing rewards – pleasurable activities such as eating or sex – also process the response to drugs or alcohol. Because of this, she says, alcohol can be used as a probe to reveal how reward behavior is encoded in the brain.
You Can Lead a Fly to Alcohol – But Can You Make It Drink?
Shohat-Ophir’s investigation began with something that could be described – metaphorically – as evil matchmaking. “We paired male fruit flies with pre-mated females, guaranteeing that the males’ courtship behavior would be rejected,” she recalls. “After this rejection experience, the males were presented with two options – plain food, or food with an elevated ethanol content. The rejected males preferred the high-alcohol food, voluntarily consuming pharmacologically significant amounts.”
On the other hand, pairing males with virgin females produced sexual success – as well as a measurable reduction in male flies’ alcohol-seeking behavior. This shed light on how social experiences are encoded on the molecular level.
“Molecular analysis of the flies that displayed a strong appetite for alcohol revealed low levels of a neuropeptide called NPF,” Shohat-Ophir says, adding that this molecular factor is believed analogous to NPY, a neuropeptide in humans. “In flies showing little interest in alcohol, the NPF level was higher. This led to another question: if we artificially manipulate NPF levels, will fruit fly behavior change? The answer, in short, was yes.”
Using thermo-genetic techniques, Shohat-Ophir artificially activated NPF neurons in virgin flies. These flies – expected to crave alcohol – adopted the tee-totaling habits of flies that mated successfully.
“By proving that the activation of NPF neurons precluded compensatory alcohol-seeking behavior, we demonstrated that NPF is the genetic ‘signature’ for the reward response,” Shohat-Ophir says, explaining that this line of research has important implications for the study of addiction. “Flies – like humans – undergo lasting genetic change as their tolerance for alcohol grows. We’re now trying to identify patterns of RNA expression and editing, in hopes of finding genes that play a central role in the addiction process.”
Shohat-Ophir’s work is currently funded by the Israel Science Foundation, as well as a European Union grant that supports world-trotting academics as they settle back into their country of origin. But a year since her return to Israel, Shohat-Ophir says that the most important support she has received is from the BIU community itself.
“I’ve found Bar-Ilan University to be a very warm and accepting place, where people are doing really good basic science,” she says. “I’m looking forward to continuing my work here for a very long time.”