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. Author manuscript; available in PMC: 2018 Jan 20.
Published in final edited form as: ACS Chem Neurosci. 2017 Aug 16;8(9):1830–1838. doi: 10.1021/acschemneuro.7b00281

Figure 2.

Figure 2

Epigenetic mechanisms supporting morphine-induced synaptic modifications in the VTA. Acute morphine increases HDAC2 activity in VTA dopamine neurons and reduces histone H3 acetylation at lysine 9 (Ac-H3K9) in the VTA 24 h following the injection. Morphine-induced synaptic changes at glutamatergic synapses involves eCB signaling to reduce GABAergic synaptic strength onto VTA dopamine neurons. Both plasticities can be recovered by a class I specific HDAC inhibitor (HDACi), through an increase in acetylation of histone H3K9. Epigenetic and synaptic modifications induced by morphine can promote dopamine neuron hyperexcitability, thereby increasing dopamine release in NAc. AKAP150 signaling controls the opposing effects of PKA and calcineurin (CaN) on GABAA receptor trafficking in the VTA. We assume that AKAP is a target for HDAC2-mediated transcriptional changes. Tilted ⊥ means inhibition. DA, dopamine; Ac, acetyl group; HDAC, histone deacetylase; HAT, histone acetyltransferase.