New Study Explains Mechanisms of How Cocaine Affects DNA to Elicit Long Term Behavioral Changes

A new research published in the May 14 issue of the journal Neuron explains how cocaine affects gene expression in the reward center of the brain in order to cause long-term behavioral changes. The said study offers a new and interesting insight into the molecular pathways that the drug regulates, thereby leading to the development of new strategies to address drug addiction treatment.

Previous studies have already established that addictive drugs can induce persistent changes in the reward circuits of the brain. There have also been studies that indicate addiction to drugs like cocaine is linked to alterations in gene expression in the brain region called nucleus accumbens (NAc). This region is associated with pleasure, reward and motivation.

“Although we have known for some time that changes in gene expression contribute to long-lasting regulation of the brain’s reward circuitry that is seen during drug addiction, how those specific genes are regulated is not well understood, explains Dr. Eric J. Nestler, the study’s senior author from the Department of Neuroscience at the Mount Sinai School of Medicine.

Dr. Nestler’s team used sophisticated gene isolation and screening methods to observe how gene transcription in a mouse’s NAc is regulated. The team also examined the regulation of the chromatin structure after cocaine is repeatedly administered.

The researchers identified a formerly unrecognized gene family – the sirtuins – which have been found to be involved in cocaine addiction manifested in this brain region. “Chronic cocaine administration was linked with an increase in sirtuin gene transcription while increased sirtuin activity in NAc neurons was associated with a potentiation of the rewarding effects of cocaine.” Inhibiting the action of sirtuins in this area also appeared to lessen the rewarding effects of the drug as well as the motivation for self-administration (of cocaine).

The results of the research identified a subset of genes that appear to be likely targets of cocaine. This has shed light to the mechanisms related to changes in the NAc that are induced by cocaine. “Our findings underscore the vast clinical potential of the many new gene targets identified in this study for the development of more effective treatments of cocaine and potentially other drug addictions,” Dr. Nestler concludes.

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