Table 2.
Cocaine-associated dysregulation of methylation dynamics.
| Ref | Species * | Tissue ** | Paradigm # | Withdrawal | Technology ## | Summary Finding |
|---|---|---|---|---|---|---|
| Global Methylation Level | ||||||
| [36] | M | NAc; PFC | CPP | Not reported | HPLC | Slight decrease in 5mC in PFC |
| [67] | M | WB | Injection | 1 h | HPLC | No differences |
| [47] | M | NAc | Injection | 24 h | LC-ESI-MS/MS | No differences in 5mC nor 5hmC |
| Cocaine Methylome | ||||||
| [53] | M | PFC | Injection Self-Admin | 0–2 h | MBD-seq | distinct patterns of DNA methylation after active and passive cocaine |
| 29 persistent DMRs after self-administration (↑ 24 and ↓ 5) | ||||||
| [47] | M | NAc | Injection | 24 h | hMeDip-seq | 5hmC alterations at enhancer regions and alternative spliced sites |
| [38] | R | NAc | Self Admin | 1 or 30 days | MeDip-Array | Dynamic (hypo and hyper-) methylation after 1 day withdrawal |
| Locus-specific enhancement or reversal of early methylation changes after 30 days | ||||||
| Cue-reinstatement reversal of many withdrawal induced changes | ||||||
| [68] | R | PFC | Self Admin | 24 h | MBD-seq | More hyper- than hypomethyated DMRs at higher differential methylation ratios |
| Differentially Methylated Loci | ||||||
| [32] | M | NAc | Injection | 24 h | MeDip Bis-qPCR | ↑ PP1c promoter methylation after acute and chronic cocaine |
| 1.5 h | MeDip-qPCR | ↓ fosB promoter methylation after acute and chronic cocaine | ||||
| [69] | R | Striatum | Injection | 15 h | Bis-seq | ↑ Cdkl5 promoter methylation |
| [37] | R | NAc | Self Admin | 0 h | Bis-seq | ↓ c-Fos promoter methylation |
| [70] | R | CC | Self Admin | 30 days | Bis-seq | ↓ Sox10 promoter methylation |
| [33] | M | NAc | Injection | 24 h | MeDip-qPCR | ↑ Scl17a7 and Cck promoter methylation and ↓ Gal, DNMT3a and DMNT3b promoter methylation |
| [71] | R | CPu | Injection | 12 h | MeDip-qPCR | ↑ PP1Cβ promoter methylation after chronic cocaine |
| [48] | M | Microglia | Injection | 1 h | Bis-seq | ↑ Mir124 promoter methylation |
| [72] | M | NAc | CPP | 2 h | Bis-seq | ↓ BDNF IV promoter at single CpG |
* M = mouse; R = rat; ** NAc = Nucleus Accumbens; CPu = caudate and putamen; PFC = prefrontal cortex; WB = whole brain; CC = corpus callosum; # CPP = conditioned place preference; ## HPLC = high performance liquid chromatography; LC-ESI-MS/MS = liquid chromatography-electrospray ionization tandem mass spectrometry; MBD-seq = methyl-binding protein capture–sequencing; MeDIP = methylated DNA immunoprecipitation; hMeDIP = hydroxymethylated DNA immunoprecipitation; Bis-seq = sodium bisulfite conversion-sequencing; qPCR = quantitative polymerase chain reaction.