Unexpected experimental results indicate nicotine creates a chronic drug memory in the brain

February 3, 2017 by Margareta Gustafsson Kubista, University of Gothenburg
Unexpected experimental results indicate nicotine creates a chronic drug memory in the brain
Credit: University of Gothenburg

In a recent study involving nicotine-addicted rats, the first period of nicotine abstinence proceeded as expected. The surprise came after three months, when the lab rats suddenly became fearless and sought out well-lighted areas that prey animals normally avoid. At the same time, signaling in the brain's reward system changed, as shown by a study at Sahlgrenska Academy.

"This indicates very long-lasting changes caused by nicotine that were previously unknown. The nicotine appears to create a cascade of effects that only get worse and worse over time," says Julia Morud Lekholm, researcher in addiction biology at the Institute of Neuroscience and Physiology.

The experiment was done another two times. The researchers wanted to make sure that the unexpected results were not an isolated case. In total, 108 animals were tested, of which half received nicotine and half a salt solution over a three-week period. The outcome was the same every time.

"The nicotine treated animals spend much more time in these more frightening areas compared with those that only received salt solution injections. We don't see this right after the nicotine treatment, only after three or more months into abstinence. So then the animals have not received any nicotine for three months, and suddenly they demonstrate an increased spontaneous impulsiveness, which is very strange," says Julia Morud Lekholm.

Strong impact

"What's interesting is that at the same time, we also begin to see changes in the GABAergic system in the brain, which is the system that normally slows the brain's signaling," she continues.

After another four months, the GABA system in the studied region of the rats' brains was so strongly affected that it had been completely reversed. Instead of dampening the nerve cell signaling, it increased it.

In other words, the results indicated a highly activated system, and an extensive risk of relapsing into smoking if human progression is similar to the rats, for example.

"Of course, rats and people are very different, but in terms of the type of brain circuit that we study, the brain's reward system, we are very much alike. Also in terms of risk-taking behavior, it's possible to translate to humans to some extent. Having isn't good for life in general, of course. One can end up in many bad situations and this may also have effects on the consumption of other drugs later in life," says Julia Morud Lekholm.

Lifelong struggle

Even if the time aspects are not directly transferable to humans, she believes the changed signaling in the to some extent explains part of the difficulties and long-lasting problems many who want to quit smoking, or using tobacco have.

"It's a life-long struggle. We understand this when we look at animals who after such a long abstinence from still have a lot of changes in their . Therefore, more efforts should absolutely be made on this kind of research to try to find new therapies, because it's extremely hard for people to be able to withstand the urge for longer time periods," says Julia Morud Lekholm.

Explore further: Study reveals how smoking increases vulnerability to alcohol abuse

More information: The thesis is available online: gupea.ub.gu.se/handle/2077/48662

Related Stories

Study reveals how smoking increases vulnerability to alcohol abuse

July 18, 2013
Smoking is a well-known risk factor for subsequent alcohol abuse, but the mechanisms underlying this link are unknown. Now researchers reporting in the Cell Press journal Neuron on July 18 show in a study conducted in rats ...

Scientists find that nicotine use increases compulsive alcohol consumption

April 14, 2015
Why do smokers have a five to ten times greater risk of developing alcohol dependence than nonsmokers? Do smokers have a greater tendency toward addiction in general or does nicotine somehow reinforce alcohol consumption?

Helping ex-smokers resist the urge

October 22, 2012
A new inhibitor helps previously nicotine-addicted rats stay on the wagon, according to a study published on October 22nd in the Journal of Experimental Medicine.

Understanding the role of genes in smoking addiction, nicotine withdrawal

October 18, 2016
Thomas Gould hopes to better understand how genes influence nicotine-withdrawal symptoms in order to develop more effective smoking cessation programs.

Recovery of dopamine function emerges with recovery from smoking

July 28, 2016
A new study in Biological Psychiatry reports that smoking-related deficits in brain dopamine, a chemical implicated in reward and addiction, return to normal three months after quitting. The normalization of dopamine systems ...

Belief about nicotine content in cigarette may change brain activity, craving

September 13, 2016
How the brain responds to nicotine depends on a smoker's belief about the nicotine content in a cigarette, according to new research from the Center for BrainHealth at The University of Texas at Dallas.

Recommended for you

Living the high life: How altitude influences bone growth

June 19, 2018
High altitude is a particularly challenging environment—the terrain is physically challenging and the land has a relatively poor crop yield, so food can be sparse. Most importantly, oxygen levels are lower meaning that ...

Introduction of alcohol found to adversely impact fertility rates in hunter-gatherer community

June 19, 2018
Fernando Ramirez Rozzi, a research director with the French National Centre for Scientific Research has found that the introduction of alcohol to a Baka pygmy hunter-gatherer society caused fertility rates to fall. In his ...

Risks of cancer and mortality by average lifetime alcohol intake

June 19, 2018
The risk of mortality, and of developing a number of cancers, is lowest in light drinkers consuming an average of less than one drink per day across their lifetime, and the risk of some cancers increases with each additional ...

Bad habits that lead to cancer, chronic disease corrected by simple lifestyle intervention

June 19, 2018
Does this sound like someone you know? He or she spends too much time in front of screens, gets little exercise and eats a diet high in fat and low in fruits and vegetables.

Graphic warning labels linked to reduced sugary drink purchases

June 18, 2018
Warning labels that include photos linking sugary drink consumption with obesity, type 2 diabetes, and tooth decay, may reduce purchases of the drinks, according to a new study by researchers from Harvard T.H. Chan School ...

Greater levels of vitamin D associated with decreasing risk of breast cancer

June 15, 2018
Researchers at University of California San Diego School of Medicine suggest higher levels of vitamin D are associated with decreasing risk of breast cancer. Their epidemiological study is published in the June 15 online ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Origin314
not rated yet Feb 06, 2017
I smoked for 22 years, I tried to quit for 15 of those 22 years via every available method with the help of support groups and encouragement from my family. I would go 1-3 months cigarette free but would inevitably return to smoking usually ending up more addicted than I ever was before especially after using NRT's

By early 2015 I was smoking more than ever, a normal day 40-60 king size cigarettes, my health was deteriorating at a quick pace, I couldn't run, I'd avoid places with stairs, after about 25 serious quit attempts given up on quitting, I knew I would die from it. One night that consisted primarily of alcohol consumption I smoked 75 cigarettes, the next morning I couldn't breathe, literally I woke up breathless, after forcing a cough I expelled 5ml of tar and could breathe.

In the face of death I had an epiphany, nicotine maintenance instead of abstinence was the only answer, I looked into vapor products, bought one and have been smoke free since March 1st 2015.

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.