NRSC 2100 Blog

Thursday, Friday, and Saturday night... I know what you're thinking. No class till Monday, no work, what a great night to get ahead on studying and up to date with all the problems in the world. However, I must point out this plan is not the first thing that pops into everyone else's mind (at least those outside the world of the poor soul who is reading this neuroscience blog). Much of western society is based around the beverage/drug/poison we've come to know as alcohol. It has come to the attention of neuroscientist that our race is not the only one that takes pleasure in consuming firewater. It turns out some researchers were playing with the old 160 proof lab ethanol when they came upon an astounding discovery.

It all started when one turned to the other and croaked, "I'm drunkk frog haha." The other slurred back, "weelll thenn, gooood thing I'm not a fly huh?" That's when it hit them. "Eureka!" piped the first. "Oh my god!" yelled the second. "Let's" get the flies wasted!" the second hollered back. They quickly spun off their lab stools and bustled for the fly room stumbling and tripping the whole way. When they got to the room they immediately grabbed the first beaker of flies, ripped out the cork and filled it full of the powerful booze, instantly killing all the flies inside. Once they realized the horrendous massacre they had just committed in front of all the hundreds of thousands of other flies in the room their drunken smiles slipped off. The beaker was placed on the counter as the two somber scientists held each other with silent tears streaming down their cheeks. Then one started laughing; irritated, the other muttered, "How can you laugh at a time like this? We just killed them, in front of their families... drowned them, squashed them like flies... "Look, that one's drunk," the other researcher pointed at a fly that was clearly not adhering to the standard sober drosophila flight pattern. They watched the fly for nearly two hours, they sat on the fly room floor entranced by the fly's drunken escapades. Then as its flight pattern began to return to normal it headed back to the beaker full of booze, and began gulping down, without a thought to the dead brothers, sisters, cousins and children floating on top. Gleeful laughter burst from the researchers as they cheersed and began taking large quaffs of their own. Quickly forgetting their bloody hands they then began pulling the corks of the other beakers, filling up petri dishes with ethanol, and pipetting small volumes of ethanol in for the larvae--so no one was left out. They spent the whole night at the lab with their new found drinking buddies and had a gay old time. A few days later after their handover was gone they decided to write a paper.

It was determined drosophila liked the inebriation caused by excessive consumption of ethanol. Like us, the flies were experiencing their pleasure through the activation of the dopamine pathway. Activating this pathway induced LTP in the flies. Looking further into the flies' neural circuitry the researchers determined the rewarding memories the flies experienced (or the lack of memory if they got too plastered from not getting enough sugar before) were localized, accessed and retrieved with a distinct set of neurons in the mushroom body. With the vast number of flies they got drunk the researchers' found some flies didn't come back to drink. The experimenters were obviously offended and quickly squashed them. However, they didn't stop there; they proceeded to analyze the DNA so they could breed out the bad gene and make sure no other flies would be lame. They found mutations in scabrous were responsible. They commonly call it the party pooper gene around the lab. "This gene encodes a fibrinogen-related peptide that regulates Notch signaling, disrupted the formation of memories for ethanol reward" (Kaun, 2011). The experimenters have been thought to have had a little bit too much fun drinking with the flies, but they have felt the public pressure. Now they're looking into how this research will help their own species and we will undoubtedly be hearing more from them soon.

Hope you enjoyed the read, sincerely Charlie Stewart

"A Drosophila model for alcohol reward"
Karla R Kaun, Reza Azanchi, Zaw Maung, Jay Hirsh & Ulrike Heberlein
Nature Neuroscience April 17th 2011

Alcoholism to this day is one of the most deadly and chronic diseases, that is interestingly controversial with regards to symptoms, treatment, diagnosis, and even heritability. How can a disease be so dangerous and historical and yet not even be remotely understood? As medicine, science, and technology move forward we are rapidly moving towards this inconceivable goal, but treatment is still only moderately successful along with progressive pharmacotherapies for all addictions.

A huge part of this lack of understanding of this disease is the fact that alcoholics are all different in a variety of ways; including their symptoms. There are numerous biological mechanisms as a result of alcohol addiction, all of them varying in their manners and withdraw. So recent studies show that these different mechanisms represent different stages of alcoholism, which could be relieved by different treatments. Regardless, these treatments have to block motivation to seek and consume alcohol.

Researchers have determined two categories: relief and reward drinkers. Reward drinkers drink to reward themselves the same way many drugs work, by activating brain reward pathways. Relief drinkers drink to relieve negative emotions, such as anxiety and feelings of withdrawal. Obviously these two varying types of alcoholics require different treatments.

It has also been discovered that alcoholism is marginally heritable. Genetic susceptibility is an alcoholic trait that can be passed down from generation to generation, however these varying types of alcoholism are largely based on environmental factors. These would include things such as how often the individual is exposed to stress or put in a circumstance of reward.

So now, is it possible to treat either one or both of these forms of alcoholism? Studies show that the reward system of alcoholism is mediated by a collaboration of endogenous opioids and dopamine release. Activation of dopamine in the mesolimbic pathway has been correlated to many other sorts of drug addictions. Dopamine is regulated in the corticomesolimbic system by a receptor known as MOR (mu-opioid receptor), which if blocked, prevents dopamine release caused by alcohol consumption. A drug known as naltrexone is an antagonist of opioid receptors, and is currently being researched as treatment for reward alcoholics.

Next is relief drinking. Relief drinkers drink to suppress stress, anxiety, discomfort, pain, and dysphoria. These alcoholics generally end up setting the stage for routine and frequent alcohol consumption to escape negative emotions. Recently, it has been discovered that release of CRF is central to this behavior. CRF (Corticotropin-releasing factor) is a peptide that is released into the anterior pituitary by alcohol consumption in relief drinkers, which in turn releases ACTH and stimulates cortisol release, reducing stress. CRF regulation and function is somewhat genetically determined, which makes a pharmacological cure more difficult and less likely to be successful. However, studies have shown that in individuals with naturally decent regulation of CRF could likely be treated for relief alcoholism; via CRF1 antagonism. Research is still ongoing as to whether this would be a sufficient method to treat alcoholics.

Alcoholism is a very complex disease, by which human understanding is challenged and pushed to therapeutic limits. This blog marks a tremendous step in the right direction towards understanding alcoholism and possibly curing the disease one day, but until that day comes there is plenty more to learn and to gain.

Heilig, Markus, David Goldman, Wade Berrettini, and Charles P. O'Brien. "Pharmacogenetic Approaches to the Treatment of Alcohol Addiction : Article : Nature Reviews Neuroscience." Nature Publishing Group : Science Journals, Jobs, and Information. 20 Oct. 2011. Web. 02 Dec. 2011. .

http://www.nature.com/nrn/journal/v12/n11/full/nrn3110.html