User:Heise123/Epigenetics of Addiction

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Epigenetics of addiction is the study of the epigenetic changes on the genome that are caused by external factors or are inherited and the development of addiction. When drugs are taken for an extended period, it causes genetic modifications that affect neural pathways in the brain. Investigating these epigenetic modifications will give more insight into the genetic basis of addiction.

Long-term drug use changes the chromatin structure in the brain, and it is hypothesized that these changes lead to addiction pathogenesis in the cell. To understand the effects of the epigenetic changes and develop further treatment, there must be more investigation into the specific modifications made to the DNA, which includes histone post-translational modifications (PTMs). Histone PTMs can alter the DNA in numerous ways, including acetylation, methylation, and phosphorylation. When continued drug abuse occurs, it can disturb the balance of histone PTMs, especially in the brain regions, like the nucleus accumbens and the midbrain ventral tegmental area. To further this point, the use of psychostimulants, nicotine, alcohol, and opiates all lead to the increased acetylation in histones, H3 and H4. This increased acetylation affects the function of HATs and HDACs, which are important enzymes that regulate histones. HATs are histone acyltransferase, which helps acetylate histones. HDAC are histone deacetylases, which reverses histone acetylation. For example, cocaine use induced increased histone acetylation in the nucleus accumbens by recruiting more HATs. Cocaine and alcohol use also decreases the activity and localization of HDACs.

Particularly in alcoholism, the amygdala epigenome is very affected by chromic alcohol use. The epigenetic changes in the amygdala show to be the cause of the negative affective state of addiction, which include anxiety and dysphoria. The initial use of alcohol use has a antianxiety effect be cause the exposure causes increased histone acetylation, increased CBP levels, and HDAC inhibition. However, the withdrawal of chronic exposure causes a decrease in histone acetylation, increased HDAC activity and decreased in CBP levels in the amygdala. These genetic modifications lead to increased anxiety behavior during withdrawal. Additional studies also showed that increased activity of HDAC2 lead to overall decreased histone acetylation in the amygdala. This caused a decreased in expression of synaptic plasticity genes, which resulted in the continuation of high anxiety behavior and high alcohol consumption.