A research team from the Icahn School of Medicine at Mount Saini reports new discoveries relating to the molecular causes of heroin addiction that, according to their additional work on rodent models, may point the way to new and promising therapeutic tools for opioid use disorder in humans. The study found that heroin use is associated with excessive histone acetylation that regulates gene expression, and that levels of hyperacetylation rise with more years of heroin use. The authors report that heroin appears to alter accessibility to portions of DNA to be either open or closed, controlling the on/off state of genes that are associated with addiction. The findings are published in the April 1 edition of Biological Psychiatry.
The team examined postmortem brain tissue from 48 heroin users and 37 controls, and identified acetylation changes at genes that regulate the neurotransmitter glutamate, which is known to control drug seeking behavior. Study author Yasmin Hurd, PhD, stated, “Because epigenetic impairments are physical alterations to the DNA that do not change the sequence of a gene, they have the potential to be reversed, so our next step was to address this possibility.” The team treated heroin addicted rats with the compound JQ1 that inhibits the readout of acetylated epigenetic proteins, and observed a reduction in heroin self-administration in the test subjects. The authors conclude that JQ1 and similar compounds may have applicability for the treatment of human heroin use disorder. John Krystal, MD, editor of Biological Psychiatry, commented, “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.”
Read more about the findings here.
The journal abstract may be read here.
Posted on March 24, 2017