- Nov 2020
To test that hypothesis, the researchers genetically modified H3 histones in rats by replacing the amino acid that dopamine attaches to with a different one it doesn’t react with. This stops dopaminylation from occurring. Withdrawal from cocaine is associated with changes in the readout of hundreds of genes involved in rewiring neural circuits and altering synaptic connections, but in the rats whose dopaminylation was prevented, these changes were suppressed. Moreover, neural impulse firing in VTA neurons was reduced, and they released less dopamine, showing that these genetic changes were indeed affecting the brain’s reward circuit operation. This might account for why people with substance use disorder crave drugs that boost dopamine levels in the brain during withdrawal. Finally, in subsequent tests, the genetically modified rats exhibited much less cocaine-seeking behavior
Rats were genetically modified to decrease dopaminylation (modifying M3 so dopamine couldn't attach). This correlated to the Ventral Tegmental Area firing less (less cocaine impulse) and released less dopamine. This showed that these changes to H3, and subsequently the dopaminylation, did impact brain's reward circuit operation.