Understanding the Epigenetics of Heroin Addiction
Heroin use and addiction may be related to excessive histone acetylation within the brain, according to a new study in Biological Psychiatry. This research is the first to provide direct evidence of epigenetic alterations within the human brain as a result of opiate use.
Opiate addiction is becoming a big problem, with an estimated 30,000 Americans dying from overdoses in the USA alone each year. Despite the prevalence of the addiction however, very little is currently known about the molecular underpinnings that define the biological implications of addiction.
To try to better understand how addiction affected a user’s brain, the team examined post-mortem human tissue from the brains of 48 heroin users and 37 non-users. They focused their attention on the striatum, a critical part of the motor and reward systems that has been implicated in addiction before because of its role in habit formation and goal-orientated behaviour.
They found that opiate use was frequently associated with excessive histone acetylation, an epigenetic process involving binding an acetyl group to a histone amino acid to regulate gene expression. The results also showed that people who had been using heroin for longer displayed greater levels of hyperacetylation. These epigenetic changes were primarily observed within genes involved in the regulation of glutamatergic function, specifically GRIA1, a glutamate receptor gene. GRIA1 has previously been associated with drug use.
The epigenetic changes observed reflect changes involved in increasing the accessibility of chromatin. This process enhances gene transcription which suggests that the impairments might play a central role in addiction behaviour.
“At this time, when prescription opioid use and opioid overdoses are both major threats to our public health, it is important to identify new treatment targets, such as epigenetic processes, that help to change the way that we do business in treating opioid use disorders,” said Professor John Krystal, Editor of Biological Psychiatry.
The team behind this research used their initial findings to move the investigation towards potential addiction treatment pathways.
“Epigenetic marks are physical alterations to the DNA that do not change the sequence of a gene, and thus have the potential to be reversed,” said Yasmin Hurd, Ph.D., lead researcher of the study and Director of the Centre for Addictive Disorders at the Icahn School of Medicine, Mount Sinai.
Using a rat model of heroin addiction, the team treated addicted rats with JQ1, a compound initially developed as an anti-cancer agent by inhibiting acetylation. They found that JQ1 reduced self-administered heroin taking in the rats, and reduced drug-seeking behaviour in rats denied all access to the drug.
“Our findings suggest that JQ1 and similar compounds might be promising therapeutic tools for heroin use disorder,” said Dr. Hurd.