Scientists have for the first time identified the brain pathway that’s hijacked by drugs of abuse, such as cocaine or heroin. The findings, published in Science, shed new light on the physical component of substance use disorder.
Mount Sinai researchers, along with scientists at The Rockefeller University, studied how mice reacted to two different classes of drugs: cocaine, a psychostimulant, and morphine, an opioid. They discovered how individual neurons in a forebrain region called the nucleus accumbens respond to repeated exposures to cocaine and morphine, as well as natural rewards like food and water.
Researchers say that there’s a large overlap of cells that respond to both natural rewards and addictive drugs, but repeated exposure to drugs progressively disrupts the cells’ ability to function normally. The cells start focusing on drug-seeking instead of natural rewards.
“By tracking these cells, we show that not only are similar cells activated across reward classes, but also that cocaine and morphine elicit initially stronger responses than food or water, and this actually magnifies with increasing exposure,” co-first author Caleb Browne, PhD, said in a news release. “After withdrawal from the drugs, these same cells exhibit disorganized responses to natural rewards in a manner that may resemble some of the negative affective states seen in withdrawal in substance use disorder.”
The study also identified an intracellular signaling pathway, mTORC1, that facilitates the disruption of natural reward processing by the drugs, along with a gene, Rheb, that activates the mTORC1 pathway.
Scientists say that discovery could potentially lead to new therapies that target the gene.
“Through our work we have also established a landmark dataset that integrates drug-induced brain-wide neural activation with input circuit mapping from the nucleus accumbens, which could be useful to the broad scientific community conducting substance use disorder research,”co-first author Bowen Tan said in a news release.
