Epigenetics and Addiction

Epigenetics is the study of how gene expression is influenced by factors such as the environment, without altering the DNA sequence itself. These modifications play a critical role in shaping cellular function and can have long-lasting effects on health and disease susceptibility. Epigenetics becomes especially interesting when discussing addiction. Addiction is a complex, chronic disease characterized by compulsive seeking of a certain substance, despite potentially harmful consequences. It changes the brain’s structure and function and is often accompanied by an inability to control one’s behavior and a strong craving for the substance. The interesting thing about addiction is that it doesn’t affect everyone. In other words, certain people are more predisposed to develop addiction after trying an addictive substance than others. Scientists are currently trying to figure out why this is, and have found that both genetics and epigenetics play a role. 

The key difference between epigenetics and genetics, is that epigenetics changes gene expression without altering the DNA sequence. Instead it works by modifying gene expression by facilitating chemical modification to a strand of DNA. This means that the actual nucleotide sequence remains the same (so the DNA codes for the same thing), but a chemical group (e.g a methyl group) is either attached or removed, which influences whether the gene is expressed or not. Scientists have discovered that epigenetic changes like DNA methylation and DNA hydroxymethylation play a crucial role in long-term changes in brain flexibility and gene expression triggered by environmental factors. Therefore, understanding what influences these DNA modifications can provide insights into why certain individuals are more prone to addiction. 

For example, a study was conducted in 2017 where scientists trained rats to self-administer methamphetamine (METH). There were some rats that showed resistance to the negative effects or aversive consequences of the drug, while others were susceptible to experiencing these aversive effects. The rats that were resistant to drug-induced aversion had different patterns of hydroxymethylated DNA in the nucleus accumbens (NAc) compared to the rats that were susceptible to aversion. This suggests that addiction behavioral phenotypes may be linked to specific DNA modifications in the brain reward regions. In studies involving non-human primates, researchers found differences in DNA methylation in the NAc, a brain region associated with reward and addiction, that were linked to different levels of alcohol intake. These differences in DNA methylation levels correlated with varying amounts of alcohol consumed, which suggests that the pattern of DNA methylation in the NAc could serve as a potential indicator or measure of susceptibility to alcohol use disorder (AUD).

 Furthermore, it has been observed that alterations in the activity of enzymes responsible for DNA epigenetic modifications, such as DNMT and TET, have been observed in the amygdala (a brain region involved in emotion and memory) of the rats that preferred alcohol. These alterations suggest that there are specific differences in DNA modification associated with different addiction-related behaviors. Recent research differences in DNA modification associated with different addiction-related behaviors. Recent research indicates that changes in DNA methylation can occur independently of the dose of drugs, contributing to vulnerability to addiction. Overall, these findings emphasize the importance of understanding how specific DNA modifications in brain regions related to reward shape individual differences in addiction risk. By studying these differences in animal models of addiction, researchers hope to gain valuable insights into the underlying causes of addiction. 

Understanding the role of epigenetics in addiction is vital for comprehending the multifaceted nature of this chronic condition. By investigating how environmental factors influence gene expression without altering the DNA sequence, epigenetics provides critical insights into why certain individuals are more prone to addiction. This research helps unravel the intricate interplay between genetic predispositions and environmental influences, shedding light on the underlying mechanisms driving addiction susceptibility. Moreover, identifying specific DNA modifications in brain regions associated with reward and addiction highlights potential biomarkers for assessing addiction risk. Ultimately, this knowledge can inform the development of targeted interventions and treatments aimed at mitigating addiction vulnerability and improving outcomes for affected individuals. Thus, research in epigenetics holds promise for advancing our understanding of addiction and facilitating more effective strategies for prevention and treatment.

Works Cited

Cadet, J., et al. “genome-wide DNA hydroxymethylation identifies potassium channels in the nucleus accumbens as discriminators of methamphetamine addiction and abstinence.” https://www.nature.com/, 5 April 2016, https://www.nature.com/articles/mp201648. Accessed 4 April 2023.

“DNA Epigenetics in Addiction Susceptibility.” Frontiers, https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.806685/full. Accessed 6 April 2024.

Hamilton, Peter J., and Eric J. Nestler. “Epigenetics and Addiction - PMC.” NCBI, 27 June 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889055/. Accessed 6 April 2024.