Latest developments in causes and treatments



Dopaminylation, Relapse and Withdrawal

Any student of reward-seeking behavior must be fascinated by the complex goings-on described by the previously mentioned associate professor of neuroscience and pharmacological sciences, Ian Maze, Ph.D., who says,

Our study provides the first evidence of how dopamine can directly impact drug-induced gene expression abnormalities and subsequent relapse behavior.

At the words “relapse behavior,” ears should perk up. Alcoholics Anonymous would prefer that members not talk about their participation because if the person takes up drinking again, the classic 12-step program receives bad publicity. Still, the organization claims 75% success; while critics say, no way, more like 10%.

So, would the success rate be the percentage of members who have never relapsed? Or would it be the number who have relapsed but come back “to continue working toward sustained sobriety?” To help people get a better grasp on the concept of success, AA provides a number of gradations, like “27 percent of AA members stay sober for less than a year… 22 percent of AA members stay sober 20 or more years.”

This post harkens back to “Dopamine and Dopaminylation,” which appeared here a week ago. Let’s return to the previously mentioned uncredited article from Genetic Engineering & Biotechnology News, which also quotes Dr. Maze’s colleague, Ashley Lepack, Ph.D.:

The question that has always challenged neuroscientists is, what are the underlying molecular phenomena that drive increased vulnerability to drug relapse in people?… Our research is shedding valuable light on this area by identifying histone dopaminylation as a new, neurotransmission-independent role for dopamine that hasn’t been implicated before in brain pathology.

NOTE: For those who like to assimilate information through their ears, Dr. Maze also explained on the Epigenetics Podcast, in an episode titled “The Role of Histone Dopaminylation and Serotinylation in Neuronal Plasticity.”

Various publications, like, have explained all this in different sentence structures to give more people opportunities to wrap their heads around it:

[H]istone dopaminylation plays a critical role in fueling heightened vulnerability to relapse over a prolonged period of time. Specifically, accumulation of H3Q5dop in the VTA can, in effect, hijack the reward circuitry, making it difficult to distinguish between good and maladaptive behavior. The study found, however, that reducing H3Q5dop in rats programmed to undergo withdrawal from cocaine significantly reversed cocaine-mediated gene expression changes and reduced cocaine-seeking behavior.

As mentioned earlier in AddictionNews, “Dr. Pretlow posits a build-up in brain energy resulting from anticipation of reward. This urge is satisfied through indulgence, which delivers the dopamine hit. Dr. Pretlow is exploring ways to displace the energy without giving into compulsive behavior.” This is of course the point and purpose of the smartphone app BrainWeighve, which offers a number of tools for people who want to change their lives.

It is useful to have a great number of tools, of course, because not everything works for everybody. Dengue fever kills about 40,000 people each year; but on the other hand, three out of four people who catch it never even show any symptoms. The point being, not everything applies across the board, to every person. There is still, in every scientific field, a lot going on where the “why” of it can’t really be pinned down; all we can do at the moment is compile statistics and make the best guess.


“What is the AA Success Rate?,”, December 31, 2018.
“Cocaine Seeking Heightened by Dopamine’s Epigenetic Effects,” Genetic Engineering & Biotechnology News, April 10, 2020.
“The Role of Histone Dopaminylation and Serotinylation in Neuronal Plasticity,”, undated
“Novel role for dopamine that impacts gene expression related to cocaine abuse,”, April 9, 2020.

Image Copyright: Quinn Dombrowski/CC BY-SA 2.0 DEED


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