PerspectiveNeuroscience

Epigenetic tinkering with neurotransmitters

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Science  10 Apr 2020:
Vol. 368, Issue 6487, pp. 134-135
DOI: 10.1126/science.abb3533

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Summary

Dopamine is a monoamine neurotransmitter associated with movement and reward responses. The ventral tegmental area (VTA), a tiny midbrain region involved in motivation and addiction, and the neighboring substantia nigra contain most brain dopamine neurons. Dopamine neurons encode reward prediction errors (1, 2), and dopamine conveys motivational value and promotes movement at multiple time scales (3). VTA dopamine neurons are part of the brain reward circuit. A central mechanism activated by addictive drugs and addictive behaviors, such as gambling, is to increase extracellular dopamine in the regions innervated by these neurons, such as the nucleus accumbens (4). It therefore comes as a surprise that dopamine is also an epigenetic mark. On page 197 of this issue, Lepack et al. (5) show that covalent attachment of dopamine (dopaminylation) to histone H3 glutamine 5 (H3Q5dop) plays a role in cocaine-induced transcriptional plasticity. Reducing dopaminylation prevented withdrawal-induced changes in gene expression and reduced cocaine-seeking behavior in rats.

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