There’s a new fruit fly article making the rounds this week. The public loves a good fruit-flies-acting-like-us story. The take home message is that male fruit flies that are deprived of sex are more attracted to alcohol (which affects them in a way similar to humans). Fruit flies like sex! Fruit flies like alcohol! Fruit flies are just like us! Besides the fact that this is funny, who cares, right? Well, these findings have important implications for the study of addiction. Let’s dive into the science of the article to understand the connections to addiction.
Sexual deprivation and alcohol intake
The first thing the authors did was establish a behavioral test, which measured attraction towards alcohol. Flies were put into a jar and in the lid were little tubes filled with fly food (sugar and yeast) or filled with fly food spiked with 15% ethanol. The flies could choose to eat as much as they wanted of either type of food. The researchers could measure how much of the food was consumed and create a ratio, which they called the preference index. The more ethanol-spiked food was consumed, the higher the number for the preference index (in other words, the flies prefer ethanol consumption). It’s previously been shown that flies will consume more of the ethanol-spiked food, even if the food tastes bad to them.
Next the authors tested two different sets of males. In one set, the males were put into a container with many virgin females and allowed to mate for 6 hours (!) In the other set, individual males were introduced to females who had already mated and were, therefore, not receptive. In other words, these males never mated and were rejected day after day. These two groups of males were then put in the jar with the food and ethanol and allowed to choose what to consume. The males who were rejected consumed much more ethanol containing food, whereas the males who had mated ate the normal food. (The New York Times has a nice video of flies mating or being rejecting, which is associated with their article about this research.)
Is this like drowning your frustrations in a beer? Sort of. The males who had been rejected, experienced two negative things: (1) They tried to mate and were rejected. (2) They didn’t have sex. Is it the rejection or the lack of sex that drives them to drink?
The authors tested this by putting males in with decapitated virgin females. Yes, that’s right—these females were dead and lacked heads. Males will still try to mate with these females, who obviously can’t reciprocate. However, since the females are dead, they do not actively reject the males. These males who couldn’t mate also showed a preference for ethanol, so it’s not the “anger” of being rejected that drives them to ethanol, it’s just not having sex.
The authors measured levels of neuropeptide F (NPF) in their two sets of male flies, and found that males who had not mated had lower levels of NPF RNA and protein. What is NPF? Neurons communicate with each other by using chemical signals. Some of these signals are small proteins, called neuropeptides, which act as modulators of neuronal activity and are often involved in behaviors. The authors wondered if they could control the flies’ attraction to ethanol by experimentally altering the NPF levels. Males who had no sex had lower NPF and higher preference for ethanol. Therefore, one might expect that a mated male who normally does not want ethanol, could develop a preference for it, if his NPF concentration was artificially decreased.
The authors decrease NPF levels by expressing inhibitory RNA (RNAi) for that gene. RNAi is a way of decreasing expression of a gene of interest, without actually mutating the gene. Mated males who expressed RNAi for NPF (their NPF levels were decreased), had a greater preference for ethanol than the controls.
In the complimentary experiment virgin males were used who have not had sex, have decreased NPF levels and a greater preference for ethanol. In order to change their ethanol preference, the authors would need to somehow artificially increase NPF levels. Instead of doing this directly, what they did was force the neurons that would be activated by NPF into a state where they were always activated regardless of NPF levels. In other words, they bypassed the need for NPF and just activated the output cell. Virgin males with their cells artificially activated (as if there were a lot of NPF around) lost their preference for ethanol.
To summarize, mating increases NPF expression and increased NPF expression makes the flies less attracted to ethanol.
The authors go on to show that mating is rewarding to flies, as is ethanol consumption and having high levels of NPF. The NPF signal in the brain acts as a “reward” center. When fruit flies have sex, this area of the brain is activated and they feel “good” and “satisfied”. However, when the fly is unable to have sex, the reward center is under-activated and the fly fills in this lack of signals by consuming alcohol. Ethanol, as well as other drugs, also activates this reward center and brings the signaling back to normal levels. The flies which had sex don’t need ethanol, because their reward center has already been activated sufficiently. Drug abuse then might be viewed as the brain trying to get that reward signal, which for whatever reason is not being satisfied by natural stimulants such as food, sex or other social interactions.