Heroin Addiction Warps Brain's Ability to Change

SAN DIEGO -- Years of heroin addiction alter gene expression and brain plasticity, researchers reported here.

  • by Staff Writer, MedPage Today
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In a study of heroin abusers' post-mortem brains, longer duration of heroin use was associated with changes in the shape and packaging of DNA in the brain in the ventral and dorsal striatum, areas of the brain associated with drug addiction, according to Yasmin Hurd, PhD, of the Icahn School of Medicine at Mount Sinai Hospital in New York, N.Y., and colleagues.

The DNA of these patients' brains became more "open" to gene expression and overactive, which may mean that a treatment that helps "close" this gap and reduce overactivity may help temper addiction, Hurd told MedPage Today during an oral presentation at the Society for Neuroscience meeting.

Healthcare costs due to opioid abuse total around $50 billion each year, according to Hurd, and opioid abuse in particular costs 2.5 times that of other medical disorders.

She also noted that "many new heroin users were first prescription opioid users," which is already a source of discussion for CDC and FDA.

The authors "studied the human striatum to characterize epigenetic marks and genes related to synaptic plasticity, dysregulation of which is a core feature of substance use disorders," This was done through a post-mortem analysis of a collection of 31 heroin users' brains and 13 matched controls.

In the ventral striatum, they saw a "significant impairment of genes related to glutamatergic neurotransmission, as well as chromatin remodeling enzymes," which they said contributed to drug-induced synaptic plasticity of the striatum.

In the dorsal striatum, they saw no significant differences in gene expression of glutamate-related markers or in histone H3 acetylation, but noted a significant positive correlation between acetylation and years of heroin use, which "suggested that chronic heroin use leads to hyperacetylation of histone H3 that contributes to the observed gene expression impairments," as well as the drug-related synaptic plasticity.

Additionally, the epigenetic changes in DNA were associated with the "heroin-related glutamatergic dysregulation in the striatum."

They were also surprised to find that there was an inverse relationship between the openness of DNA and heroin overdose, implying that the mechanisms at work in overdose are different from those involved in addiction, Hurd noted.

Hurd cautioned that much of this research is ongoing, and that pharmacologic or other treatment targets are, at best, being looked at in animal models.

In a model of mice allowed to self-administer heroin, "the degree of the activation of glutamatergic genes related to the amount of heroin they took," she noted, so perhaps those animals and those people who have been taking heroin for a longer time and larger amount may need a longer treatment.

"Is a person injecting heroin for 10 years going to need the same degree of treatment as someone in their first year of drug abuse?," she posed as a future research target, cautioning that addiction is -- at least presently -- a life-long problem.

"We want to see if we can re-normalize the brain and see if we can give them a chance if they relapse again," she said.

The study was supported through an NIH grant.

The authors declared that they had no conflicts of interest.