Table 1.
Cocaine-associated dysregulation of DNA methylation machinery.
| Ref | Species * | Tissue ** | Paradigm | Withdrawal | Summary Finding |
|---|---|---|---|---|---|
| Methyltransferases and Dioxygenases | |||||
| [46] | M | Striatum | Injection | 4 h | ↑ Dnmt3a mRNA in D1-MSNs only after chronic injection |
| [33] | M | NAc; Hipp | Injection | 24 h | acute injection ↑ Dnmt3a/b mRNA in NAc and Dnmt3b in Hipp |
| repeat injection had no effect on Dnmt expression | |||||
| 1.5 h | acute injection ↑ Dnmt3a mRNA in NAc and Dnmt3b in Hipp | ||||
| chronic injection ↑ Dnmt3a mRNA in Hipp | |||||
| [34] | M | NAc | Self Admin | 24 h or 28 days | Biphasic expression of Dnmt3a mRNA (↓ 24 h but ↑ 28 days withdrawal) |
| Injection | 28 days | ↑ DNMT3a mRNA | |||
| [36] | M | PFC | Self Admin | 2 h | ↑ Dnmt3a mRNA and ↓ Dnmt3b mRNA and protein |
| [47] | M | NAc | Injection | 24 h | ↓ Tet1 mRNA and protein |
| H | NAc | Post mortem | N/A | ↓ TET1 mRNA | |
| [37] | R | NAc; PFC | Self Admin | 0 h | ↑ Dnmt3a/b mRNA expression in NAc only |
| [48] | M | BV-2 cells | 24 h Exposure | N/A | ↑ Dnmt1 and Dnmt3a protein |
| R | Microglia | 24 h Exposure | N/A | ↑ Dnmt1 protein and all Dnmt mRNA | |
| M | Microglia | Injection | 1 h | ↑ all Dnmt mRNA | |
| Methyl-Binding Proteins | |||||
| [49] | R | DCPu; FC; DG | Injection | 15 h | ↑ Mecp2 and Mbd1 positive cells in all areas |
| [50] | M | NAc | Injection | 2 h | ↑ phosphorylated Mecp2 |
| [51] | R | DCPu; PFC; Hipp | Self Admin | 24 h | ↑ Mecp2 protein and positive neurons in DCPu with extended access |
| ↓ Mecp2 protein a in PFC with extended access | |||||
| ↑ Mecp2 protein in Hipp with restricted or extended access | |||||
| [52] | R | CPu; Nac; PFC | Injection | 20 min | ↑ Mecp2 phosphorylation in NAc |
| 60 min | ↑ Mecp2 phosphorylation in CPu | ||||
| [53] | R | CPu; PFC | Injection/Self Admin | 5-15 h | ↑ Mecp2 expressing cells with no change in mRNA |
* M = mouse; R = rat; H = human; ** NAc = Nucleus Accumbens; CPu = caudate and putamen; DCPu = dorsal caudate and putamen PFC = prefrontal cortex; FC = frontal cortex; Hipp = hippocampus; DG = dentate gyrus.