The first cigarette I ever smoked tasted like two-week-old laundry. It also made me dizzy, spiraling me into vertigo. The second one wasn’t much different, but it was somewhat more tolerable. But by the time you get hooked, smoking actually becomes pleasurable. A new study explains why people who just started smoking feel repulsed by the act and this insight could potentially lead to new smoking cessation methods.
Taryn Grieder is a research associate and neuroscience lecturer at the University of Toronto. For the past decade, she has been investigating the addictive properties of nicotine. This kind of research has revealed, for instance, that nicotine has a dual response in the brain. On one hand, the drug generates a reward response — what we recognize as ‘pleasure’ — while, on the other, it can also trigger disgust.
This peculiar dual effect was thought to be due to the activation of nicotine receptors in different brain regions. Grieder and colleagues, however, have shown that both reward and aversion responses are generated by two different populations of neurons that are found in the same brain region — the ventral tegmental area (VTA). This midbrain region is part of the mesolimbic dopamine pathway and an important part of the “reward system.”
“Now we know that nicotine hits different populations of neurons in the same area, from which neurons project to the different brain regions,” Grieder said in a statement.
According to the new study, which was published in the Proceedings of the National Academy of Sciences, when someone tries their first cigarette, all nicotine receptors in the VTA are activated. This response stimulates both pleasure and aversion. Soon enough though, through repeated use, the brain changes and a smoker can rapidly transition from “that’s gross!” to craving the sweet release of nicotine.
“Aversion should be there all the time, but the more someone smokes, they’re going to have changes in the amounts of the receptors and in the signaling processes in the brain reward system,” Grieder said.
In order to differentiate the two nicotine-activating neural cell populations in the VTA, the researchers first studied a mouse strain that has absolutely no nicotine receptors. As such, these particular rodents don’t get a kick from nicotine, nor are they repelled by it — they’re completely indifferent to it.
These mice were infected with a virus that was engineered to introduce nicotine receptors into either dopamine or GABA neurons. The researchers then exposed the mice to high doses of nicotine comparable to heavy smoking and measured the rewarding or aversive effects of the drug using a standard behavioral test.
This experiment showed that when dopamine neurons in the VTA were active, nicotine aversion was triggered, whereas GABA neurons were responsible for the rewarding effect of the drug. This is a very rare instance where dopamine is not at all involved in the reward response, challenging the somewhat entrenched consensus that dopamine is always the main reward signal. For nicotine, at least, this doesn’t seem to be the case.
“The biggest challenge was separating the two types of neurons in the brain so that we could see which were responsible for pleasure and disgust for nicotine,” Grieder told me in an e-mail.
“The ‘aha!’ moment was when the dopamine neurons, which are commonly thought of as reward neurons, were responsible for signaling the bad feelings that nicotine leads to,” she added.
The above findings apply to non-addicted animals, though. The brains of mice that are hooked on nicotine look totally different. While dopamine neurons might be responsible for aversion in non-dependent rodents, they signal both reward and withdrawal avoidance in mice addicted to nicotine.
“When you make the switch to addiction there’s a switch in the brain’s motivational system,” says Grieder. “It’s not about getting the good feeling anymore–it’s about relieving the bad feelings of not having enough drug in the system.”
As any former smoker will attest, quitting cigarettes is very hard and relapse is common. Although there are many behavioral methods and hundreds of books on quitting smoking, nicotine replacement therapy — which gradually weans smokers off nicotine — is the only effective pharmaceutical therapy.
In the future, Grieder envisions translating her findings into a drug similar to Antabuse, which causes severe nausea when alcohol is ingested to deter alcoholics from drinking — only that it would work against nicotine. Such a drug would cause a smoker to feel incredibly repulsed by nicotine, making quitting much easier.
“We are are now looking at how social behavior in the brain is related to nicotine reward,” Grieder said.
