The molecular mechanisms underlying the persistence of addiction remain largely unclear. Lepack and colleagues found that, with cocaine exposure, there is an intracellular accumulation of dopamine in neurons of a brain region called the ventral tegmental area. Dopamine associates with chromatin to initiate a previously unknown form of epigenetic regulation called dopaminylation. This modification has an impact on ventral tegmental area function and, consequently, on dopaminergic action potentials. The result is aberrant dopamine signaling in the ventral striatum during periods of drug seeking.

Lepack AE, Werner CT, Stewart AF et al.: Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking. Science 368 (6487): 197-201 (2020).

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