Latest developments in causes and treatments



Dopaminylation — What and Why?

As we have seen, addictive drugs and dopamine go together like peanut butter and jelly. The question is, why? Neuroscientist R. Douglas Fields has written about surprises revealed a couple of years back which have continued to intrigue scientists. Part of the reason for a new understanding is that the branch of science called epigenetics does not work quite like its original discoverers believed. The author defines epigenetics as “a form of gene expression that can be inherited but isn’t actually part of the genetic code.”

As it turns out,

…[W]e really can inherit traits our parents acquired in life, without any change to the DNA sequence of our genes… Inherited genes are activated or inactivated to build a unique individual from a fertilized egg, but cells also constantly turn specific genes on and off throughout life to make the proteins cells need to function.

To explain the proteins called histones, Fields offers an analogy to spools of tape that need to be unwound in order to access their information — or in some instances, need not to be unwound. In brief, epigenetic inheritance implies not alteration of the DNA code, but of the cell’s ability to either read the code or not. The chemical signaling between neurons is, Fields says, “what enables us to think, learn, experience different moods…” Dopamine is the neurotransmitter that provides what he calls the “spurt of euphoria” — until it no longer does.

Fields writes,

Nearly all addictive drugs, like cocaine and alcohol, increase dopamine levels, and the chemically induced dopamine reward leads to further drug cravings. A weakened reward circuitry could be a cause of depression, which would help explain why people with depression may self-medicate by taking illicit drugs that boost dopamine.

Neuroscientist Ian Maze learned a lot about how serotonin does its job, and then similarly explored dopamine, specifically looking at how it regulates certain genes that appear to be involved in drug addiction and consequently, in the misery of withdrawal. The two chemicals have since been described as “double agents, acting obviously as neurotransmitters, but also as clandestine masters of epigenetics.”

The same process that turns genes on or off appears to be active in rewiring the brain’s reward circuitry and, even more interesting to addiction experts, has very much to do with the intense cravings felt by addicts during withdrawal. By extension, it could also intensely affect children who can’t keep their hands out of the cookie jar.

The brain chemical dopamine transmits signals across synapses, and it also can go into the nucleus of a cell and issue orders to specific genes. This, Fields realized, “completely upends our understanding of genetics and drug addiction.” Dopamine’s ability to control such genes might be the underlying mechanism of addiction itself, the energy that translates into the irresistible craving that can send a person out into a blizzard in the middle of the night, ready to do whatever is necessary.

For example…

Long-term cocaine use modifies neural circuits in the brain’s reward pathway, making a steady intake of the drug necessary for the circuits to operate normally. That requires turning specific genes on and off to make the proteins for those changes, and this is an epigenetic mechanism driven by dopamine acting on H3, not a change in DNA sequence.

Of course, one of the big questions for researchers in the field is, whether this epigenetic change process works with other drugs including alcohol and nicotine. More research in this direction might open up the possibility of medications that could nip addiction in the bud.

Written by Pat Hartman. First published March 29, 2024.


“The Epigenetic Secrets Behind Dopamine, Drug Addiction and Depression,” Quanta Magazine, October 27, 2020.

Image Copyright: bark/CC BY 2.0 DEED


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