One of the major challenges of cocaine addiction is the high rate of relapse after periods of withdrawal and abstinence. Now, new research from McGill University and Bar Ilan University reveals that changes at a DNA-based level during drug withdrawal may offer promising ways of developing more effective treatments for addiction. The data findings show that withdrawal from drug use results in reprogramming of the genes in the brain that lead to addictive personality. The study is published in the Journal of Neuroscience.
The team explain that genes are inherited from parents and these genes remain fixed throughout the person’s lifetime and are passed on to their children; there is little that can be done to change inherited adverse genetics changes. In contrast, state the researchers, epigenetic marks such as DNA methylation act as switches and dimmers of genes. These epigenetic tags can be switched on, off, or dimmed by epigenetic drugs inhibiting DNA methylation and removing methyl marks from genes.
The team state that they wanted to see if they could stop addictive behaviour by influencing the epigenetic markers that were triggered by withdrawal using epigenetic drugs such as the DNA methylation inhibitor, RG108.
The current study used a rat model of incubation of cocaine craving, in which rats were trained to self-administer cocaine which was cued by a specific light or sound. This drug craving or addictive behaviour was tested after either 1 day or 30 days of withdrawal from cocaine. Following the long withdrawal, the rats developed an intense drug seeking behaviour when exposed to the cue. It was after a lengthy period without the drugs that the epigenetic changes were most evident.
The results showed that the biggest changes in DNA methylation occurred not during the exposure to the drug but during withdrawal. During this period of withdrawal, hundreds of genes changed their state of DNA methylation including genes that previous studies have shown to be involved in addiction. The researchers state that the data findings may point to new avenues for treatment of addiction in humans.
The team surmise that the mainstay of current approaches to treating addiction might actually aggravate it. They go on to add that the current study results suggests that because the changes in addiction involve numerous genes, current approaches will continue to fail if too few genes are targeted in the brain, however, more research is needed to confirm if these new avenues hold promise.
Source: McGill University
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