Addiction and our Epigenome

Addicts by nature

We are all addicts in some sense. We each take some actions repeatedly, despite their perceived negative consequences. My favorite comedian is Jim Gaffigan. In my view, Gaffigan’s famous bit on McDonalds, sums this idea up.

We all have our McDonalds. Has your mother ever made anything as good as a McDonalds fry?…NOT EVEN CLOSE. I’m tired of people thinking they’re better than McDonalds. But really you have your own McDonalds. Maybe instead of buying a Big Mac, you read US weekly. Hey that’s still McDonalds. Maybe your McDonalds is telling yourself that Starbuck Frappichino is not a milk shake. Or maybe you watch Glee. Its ALL McDonalds. McDonalds of the soul. Momentary pleasure, followed by incredible guilt, eventually leading to cancer. “

So called “behavioral addiction” is just part of our human nature.

The dire straits of cocaine abuse

Unfortunately being prone to drug addictions is also very human. Cocaine abuse is especially monstrous. Taking cocaine releases the pleasure neurotransmitters dopamine, norepinephrine, and serotonin. At first the effect is bliss. Soon after, cocaine disrupts arousal, fight or flight, appetite, mood and sleep systems in the brain. All pretty miserable. Repeated use causes the gradual depletion of the neurotransmitters and dis-regulation of all these systems. The bottomless pit of addiction to this drug is profound. Lab primates with unlimited access, will take cocaine until they die with seizures. One study demonstrated that primates will push a bar 12,800 times for a single dose!

Cocaine addiction disorder is a plague to society, with associated misfortunes comparable to, or surpassing any disease. Addiction leads to numerous psychiatric and cardiovascular problems. In the USA population, almost 1/3 of homicide victims are associated with cocaine use. As are about 1/5 of suicides. Understanding the biology of addiction in order to develop treatments is critical to our health as a society. Unlike primates, our human tendency for addiction is tempered with our ability to plan our actions based on risk assessments.

Epigenetics of transgenerational inheritance

Fair M. Vassoler, Ghazaleh Sadri-Vakili Mechanisms of transgenerational inheritance of addictive-like behaviors (July 2013) Neuroscience. Explores the possible modes of how drug abuse changes the epigenome of future generations. They also present some preliminary results of their new model in rats.

The authors review relevant research results. They note examples demonstrating three modes of epigenetic mechanisms of transgenerational epigenetic inheritance. These generally include DNA methylation, post-translational histone modifications and small non-coding RNAs. They discuss other environmental stimuli shown to produce transgenerational inheritance. These include examples of behavioral or social transmission to offspring, environmental toxins, modes of stress and diet. The authors point out that these various environmental inputs likely share the same underlying epigenetic processes leading to adaption.

The group developed a model of paternal cocaine abuse in rats. Male rats were trained to self administer cocaine, and were allowed to do so for the 60 day duration of spermagenesis.  Then they were mated.  The behavioral results were that “…male, but not female, cocaine-sired offspring, demonstrate delayed acquisition and decreased intake of cocaine during adulthood … “  For people in the real world, a family history of drug addiction increases your susceptibility.  However the opposite held true in their experiments so far. I repeat, the first generation offspring (F1) actually show increased resistance to cocaine.

The scientists had previously reported that cocaine-induced increases in brain-derived neurotrophic factor (BDNF) were associated with increases in acetylated histone H3 (H3K9K14ac2) in the medial prefrontal cortex (mPFC ). In this study they found that BDNF mRNA and protein from the mPFC increased, due to increased acetylated histone H3 (H3K9K14ac2). But only in male offspring. I wonder why that is? The next test will be what happens in the next generation (F2) , the “grand-rats”, so to speak. That’s important because that generation are not produced from the gametes of the first drug addicted generation.

These ideas are all kind of wild, since we didn’t even know until recently that traits could be inherited via the epigenome. We thought the imprinting process totally cleared the genome. But instead there is an impression left from these key experiences in the previous generation. Further research will aim to work out the mechanisms behind drug resistance….and perhaps all transgenerational epigenetic adaption.

Vassoler FM, & Sadri-Vakili G (2013). Mechanisms of transgenerational inheritance of addictive-like behaviors. Neuroscience PMID: 23920159

This entry was posted in Addiction, Animal Models, Behavioral Epigenetics, Epigenome, Neuroscience and tagged , , , , , , , . Bookmark the permalink.

One Response to Addiction and our Epigenome

  1. Emmy Han says:

    Nice piece on a compelling new experiment. However, it seems a shame to diminish such work, perhaps for the benefit of non-specialized readers, by referring to dopamine, serotonin, and norepinephrine as “pleasure neurotransmitters”. Previously, monoamines, especially dopamine, have been implicated in reward, but their effects are far greater reaching and probably even still not fully understood. Furthermore, saying the offspring had “resistance to cocaine” does not pack the punch intended. Resistance to cocaine self-administration, sensitization, physiological effects? I truly applaud your coverage of the article, but perhaps it is possible to access non-specialized readers without offending the sensibilities of readers with knowledge in the area.

Leave a Comment

Your email address will not be published. Required fields are marked *


You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>