Scientists from Mount Sinai School of Medicine have hopefully developed new strategies for battling cocaine addiction by studying its links to genes and its enhancement of the behavioural effects of addiction.
The research team led by Dr Eric J. Nestler from the Department of Neuroscience at the Mount Sinai School of Medicine have provided fresh insights into the molecular pathways regulated by cocaine.
It is already known that addictive drugs induce persistent changes in the brain's reward circuits.
Previous research has indicated that addiction to drugs such as cocaine is associated with altered gene expression in the nucleus accumbens (NAc), a region of the brain that is involved in motivation, pleasure, and reward.
"Although we have known for some time that changes in gene expression contribute to the 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," said Nestler.
The research team studied the regulation of gene transcription in the mouse NAc, including regulation of chromatin structure, after repeated administration of cocaine.
The researchers also identified a previously unrecognized family of genes, called the sirtuins, as being involved in cocaine addiction in the NAc.
The study showed that 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.
The team suggests that inhibition of sirtuins in the NAc reduced the rewarding effects of cocaine and the motivation to self-administer the drug.
They identified the subset of genes that are highly likely to be targets of cocaine and shed light on the specific mechanisms that underlie cocaine-induced changes in the NAc.
"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," said Nestler.
The study appears in the journal Neuron.