Cocaine-linked genes enhance behavioral effects of addiction

May 13, 2009,

New research sheds light on how cocaine regulates gene expression in a crucial reward region of the brain to elicit long-lasting changes in behavior. The study, published by Cell Press in the May 14th issue of the journal Neuron, provides exciting insight into the molecular pathways regulated by cocaine and may lead to new strategies for battling drug addiction.

It is well established 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 contribute to the long-lasting regulation of the brain's reward circuitry that is seen during , how those specific genes are regulated is not well understood," explains senior study author, Dr. Eric J. Nestler from the Department of Neuroscience at the Mount Sinai School of Medicine.

Dr. Nestler and colleagues combined sophisticated and highly sensitive genetic isolation and screening techniques to study regulation of gene transcription in the mouse NAc, including regulation of chromatin structure, after repeated administration of cocaine. The results of this novel analysis significantly refined the understanding of cocaine-regulated gene transcription in general, and advanced knowledge of the specific role of two transcription factors known to play a prominent role in cocaine-induced addiction.

The researchers also identified a previously unrecognized family of genes, called the sirtuins, as being involved in cocaine addiction in the NAc. 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. Importantly, pharmacological inhibition of sirtuins in the NAc reduced the rewarding effects of cocaine and the motivation to self-administer the drug.

Taken together, the results identify a 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," concludes Dr. Nestler.

Source: Cell Press (news : web)

Related Stories

Recommended for you

Study finds alcohol dampens brain waves associated with decision-making but not motor control

March 15, 2018
We all know that alcohol impairs our judgement, alertness and performance on tasks requiring attention, but the mechanism behind booze's effect on cognition still isn't well-understood. Now, a new study led by psychologists ...

Breakthrough discovery in neurotransmission

March 15, 2018
Samir Haj-Dahmane, Ph.D., senior research scientist at the University at Buffalo Research Institute on Addictions, has discovered how certain neurotransmitters are transported and reach their targets in the brain, which could ...

Research reveals brain mechanism involved in language learning

March 15, 2018
Learning a new language may be more of a science than an art, a University of Sussex study finds.

New research sheds light on underlying cause of brain injury in stroke

March 15, 2018
New research shows how the novel drug QNZ-46 can help to lessen the effects of excess release of glutamate in the brain – the main cause of brain injury in stroke.

Cell therapy could improve brain function for Alzheimer's disease

March 15, 2018
Like a great orchestra, your brain relies on the perfect coordination of many elements to function properly. And if one of those elements is out of sync, it affects the entire ensemble. In Alzheimer's disease, for instance, ...

New tissue technique gives stunning 3-D insights into the human brain

March 15, 2018
Imperial researchers have helped develop a breakthrough imaging technique which reveals the ultra-fine structure of the brain in unprecedented detail.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.