Many people have had hangovers from drinking too much alcohol, and yet despite the unpleasant consequences the morning after a party, they still continue to drink. A recent study published in the journal Neuron reveals a possible cause of the phenomenon, and suggests that alcohol changes the way memories are formed, painting a more pleasant picture of memories made while under the influence of alcohol.
The Notch Pathway
Though it has been a long-established theory that alcohol and addictive drugs like cocaine alter the reward pathways within the brain, the new study hints at how those pathways may be rewired. The study, done by Brown University researchers, shows that the consumption of alcohol impacts a certain cell signaling pathway referred to as the Notch pathway.
Notch is a type of protein and this pathway, although studied in fruit fly models, is in the brains of most multicellular organisms. The Notch pathway is how many animals learn to go after pleasurable experiences. Humans have this pathway as well, and the researchers suggest that alcohol impacts the brain by activating the pathway and changing its structure.
As reported by Inverse, an assistant professor of neuroscience at Brown University, Karla Kaun, explains that the effects of alcohol on the Notch pathway contribute to the formation of memories associated with intoxication itself and that this type of association can frequently lead to addiction. In an interview with Newsweek, Kaun said that as one drinks they form memories based off of cues in their environment. These experiences, like the taste or smell of wine, become associated with a general feeling of intoxication.
“Our study provides genetic and biochemical evidence that fairly low doses of alcohol can activate a highly conserved cell-signaling pathway in the brain, leading to changes in expression of genes important for learning and memory,” said Kaun.
As for exactly how alcohol impacts the Notch pathway, is suspected that alcohol creates altered gene expressions within the pathway. The Notch signaling pathway plays a critical role in the brain of an embryo as it develops, setting up systems for learning and reward. However, the study implies that the Notch pathway could have a major impact on the brain of adults as well, not merely embryos and the still-developing brains of children. The Notch pathway could have a substantial influence on how alcohol kicks off the use of dopamine within the brain. Dopamine is not merely associated with good feelings and warm memories, it is also associated with addiction.
Analyzing Chain Reactions
Fruit flies were used as a model by the researchers because of their comparatively simple brains. While humans have around 100 billion neurons in their brain, the brains of fruit flies have only around 100,000 neurons making them orders of magnitude smaller. Scientists have developed many different tools to alter the activity of these neurons at the molecular level over the years, which gave the research team an excellent model to examine how both molecular signaling pathways and genes influence the creation of memories while the brain is impacted by alcohol.
As reported by ScienceDaily, the researchers were able to use their genetic toolkit to turn certain genes on and off while they tried to train the flies to find alcohol in a lab. The ability to alter the expression of these genes let them determine which proteins were necessary for the reward-seeking/association behavior to begin.
The Notch pathway is a signaling pathway that is built out of a system of cascading inputs and outputs, with Notch being the first “domino” that kicks off the chain reaction. When Notch is activated it triggers the activation of the next molecular signals, which trigger the next signals, and so on. Somewhere in this pathway is a gene referred to as dopamine-2-like receptor, which is responsible for the creation of a protein found on neurons that receives and recognizes dopamine. According to ScienceDaily, postdoctoral researcher Emily Petruccelli explained that dopamine-2-like receptor is involved in the encoding of memories, and it affects how a memory is perceived – whether it is aversive or pleasing in nature.
So not only was the Notch pathway activated in the brains of fruit flies who had been trained by the researchers to be attracted to alcohol, the activation of the pathway led to a number of different cascading effects. Among these effects was a change to the expression of the gene known as dopamine-2-like receptor. It is important to note that the alcohol only changed how dopamine receptors were expressed, it didn’t decrease the production of dopamine receptors or increase them. The change to dopamine-2-like receptor was quite subtle in nature, changing just one amino acid letter in an important area of the gene, but the impact of this change could have significant consequences. Kaun explained:
One of the important findings from this study is that scientists need to look not only at which genes are being turned on and off, but which forms of each gene are getting turned on and off We think these results are highly likely to translate to other forms of addiction, but nobody has investigated that.
Towards A Greater Understanding Of Addictive Substances
The authors of the study state that the alcohol is essentially hijacking the dopamine pathways within the brain, altering the way that the pathways responded to reward and pleasure. According to Kaun in an interview with The Independent, one glass of wine is likely enough to activate the Notch pathway, although within an hour the pathway returns to its baseline state. Kaun said that the effect is amplified the more alcohol one has and that after three glasses of wine the pathway won’t return to its normal state for a full day. Kaun explained that it is likely the persistent effects of alcohol are what alter the gene expression of memory circuits.
It is hoped that a better understanding of how alcohol impacts the brain, how it alters memory and reward pathways at the level of the cell could lead to the development of better treatment methods for those who struggle with substance abuse.
In the meantime, the research team will continue working on how the reward pathways of the brain are influenced by addictive substances, hoping to determine how changes at the level of the gene/cell can contribute to the addictive nature of some drugs. The research team is currently working on a project that investigates how opiates affect the same reward pathways. Kaun will also be working with psychiatrists and human behavior specialists to analyze DNA samples taken from patients with alcohol abuse disorders. The goal will be to discover if the patients have any variations within the craving-related genes that were discovered in this past study.
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