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Single Cocaine Dose Rewires 3D Genome in Mouse Midbrain Cells

If confirmed, the persistent structural shifts could help explain how an initial exposure raises the brain's sensitivity to later cocaine use.

Overview

  • Researchers led by Ana Pombo presented Tuesday at the FENS Forum 2026 that one cocaine exposure in mice changed the three-dimensional folding of DNA in ventral tegmental area dopaminergic neurons.
  • The team used genome architecture mapping and reported about 1,700 newly formed and 1,100 lost chromatin insulation areas, with many changes apparent 24 hours after exposure and still present or larger two weeks later.
  • Exposed neurons showed altered gene activity, including higher expression of several neuropeptides linked to addiction and reduced activity of genes tied to normal cell function.
  • The findings are preliminary because they come from a conference presentation in mice and researchers plan longer-term studies and cross-species tests to measure how durable the changes are and whether they affect addiction risk in humans.
  • The work connects a molecular mechanism to public health concerns about cocaine use worldwide and could point to targets for future treatments if the results hold up in further experiments.