Until now, it has been thought that drug addiction results from two separate systems in the brain: the reward system, activated when a person uses a drug, and the stress system, activated during withdrawal. But a new study suggests there are specific neurons in the brain's reward system that are active during both use of and withdrawal from nicotine.

Person smokingShare on Pinterest
Researchers found that neurons in the reward system of the brain are active during both use of nicotine and withdrawal, suggesting that targeting these neurons could reduce both the high produced by the drug and withdrawal symptoms.

The researchers, led by Olivier George, assistant professor at The Scripps Research Institute (TSRI) in San Diego, CA, say they think these same neurons may be active in response to other addictive substances. Their study is published in the journal Nature Neuroscience.

"If we can find a way to target those neurons in humans," explains George, "maybe we can reduce the 'high' produced by the drug and reduce the withdrawal symptoms."

He says he hopes their study will aid drug development or the creation of genetic therapies to target the neurons.

The researchers explain that previously, the ventral tegmental area (VTA) - an area of the brain where the neurons are found - was only associated with the reward system and not with withdrawal stress. It was known that these VTA neurons produce dopamine, which is a neurotransmitter linked to pleasure.

However, 5 years ago, when George was collaborating with a staff scientist at the University of Toronto, they detected a stress peptide in the VTA. The stress peptide in question is called corticotropin-releasing factor (CRF), which is associated with anxiety and depression.

After running the test two more times, the team came up with the same result.

CRF-producing neurons in the VTA activated during withdrawal

After these surprising results, George and colleagues from the Salk Institute in La Jolla, CA, looked more closely at the VTA, using radioactive RNA markers to observe CRF in rodent brain samples.

After not finding anything out of the ordinary, one day, the team saw tiny black dots on the X-ray film; these were the CRF-producing neurons found in the VTA.

"If you look in a textbook," says George, "these neurons don't exist in the VTA. That was the most exciting day of my career."

Next, the team looked at the role these neurons play in nicotine addiction by studying brain samples of mice and rats that had been made to develop nicotine dependence equivalent to a human who smokes two packs of cigarettes a day.

Results revealed that the CRF-producing neurons in the VTA were activated during withdrawal, and upon examining brain samples from humans, the team found that these same VTA neurons are present.

Previous studies have shown that rodents and humans who have relapsed from quitting smoking often consume more nicotine than they did when first exposed to it. As such, the researchers tested whether CRF production in the VTA was linked to this behavior by targeting a gene in the neurons to decrease CRF production during withdrawal.

Results from this test showed that rodents with less CRF in the VTA did not increase their nicotine intake during a subsequent course of access to the substance.

Commenting on their findings, George says:

"That changes the whole conceptual framework. We have to look at everything again, going back to the 1970s. It's possible that when you activate those neurons, you have the reward system that's activated - you have this euphoria, this high - but at the same time you activate this stress peptide."

He adds that, now that they have found a connection between the reward and stress systems, he thinks of both systems working together as one "motivational system," whereby the dopamine high drives a person to keep smoking, while the stress of withdrawal encourages them not to quit.

Medical News Today recently reported on a study that suggested cigar smoking is just as harmful as cigarette smoking.