Drugs used in manipulating DNMT activity and affect DNA methylation patterns have shown promise in both in-vitro and in-vivo models to dissect neuronal function. Two DNMT inhibitors, zebularine and 5-aza were used to modulate LTP induction, synaptic plasticity and learning and memory behaviors in the hippocampus (Levenson et al., 2006; Lubin, Roth, & Sweatt, 2008). Zebularine and 5-aza have been used to study cocaine-regulated phenotypes and have been used to delay the onset of cocaine sensitization and attenuate cocaine reward respectively (Anier et al., 2010; Han et al., 2010). In an excessive alcohol-drinking paradigm, 5-aza was able to reduce excess ethanol intake in mice (Warnault et al., 2013). Newer direct DNMT catalytic activity inhibitors, such as the pan-DNMT inhibitor RG108 have been developed and have been successfully used in regulating remote memories (Miller et al., 2010).
