October 07, 2005
Nicotine Leaves Long Lasting Effects On Brain Reward Systems

Scripps researchers Athina Markou and Paul Kenny found that in rodents nicotine causes an elevation in mood that lasts for weeks after the nicotine is gone.

Nicotine induces a long-lasting activation of the brain's reward systems that is not seen after excessive consumption of other drugs of abuse, such as cocaine or heroin. This slight elevation in mood is there regardless of how much nicotine is consumed, and it persists long after the nicotine is gone from the body.

"It's almost a memory of nicotine in the brain," says Kenny, who is now a staff scientist at Scripps Florida. "The reward system becomes hyperactive, even when the nicotine isn't there."

This persistence of reward activity, Kenny adds, appears unique to nicotine among drugs of abuse and is probably crucial in maintaining the nicotine habit. Knowing this may have relevance to prevention of nicotine addiction and smoking cessation programs.

Weeks after the nicotine was gone the effects on rodent brain reward systems remained. Normal pleasures were still enhanced by the long gone nicotine.

In their study, Markou and Kenny looked at the effect of nicotine self-administration on brain reward systems in laboratory rodents. They allowed the rodents to have extended access to nicotine self-administration, and they directly measured the changes in neuronal activity in the brain.

As predicted, the scientists found that nicotine acutely stimulates the brain's reward system and seems to enhance the normal pleasures in the environment for hours. Unexpectedly, however, rather than the depression-like state induced when cocaine and heroin leave the system, nicotine's elevation of mood persists. The measurements of neuronal activity in the brain's reward system one hour after the nicotine consumption looked similar to those twelve hours after consumption.

In fact, this increased sensitivity to reward persists for days or weeks after the nicotine disappears. The excitation of these systems cannot be due to the presence in the brain of nicotine, which is readily metabolized by enzymes in the body so that all traces of it are gone after a matter of about three to four hours.

So if the nicotine is metabolized and cannot be responsible for the elevation in mood, what is the explanation? One possibility is that nicotine leads to an upregulation of the brain receptors to which it binds--the nicotinic receptors. Since the neurotransmitter acetylcholine also binds to these receptors, the elevation in nicotinic receptors due to nicotine may be behind the persistent elevation in mood.

Do addicts of the demon weed tobacco experience increased pleasure from life as a result of smoking tobacco? Had they never started smoking would their average level of experience of pleasure be lower?

What I'd like to see: A study of twins in their 20s (i.e. young enough not to have too much accumulated damage from cigarette smoking) where one member of each twin smokes and the other doesn't. Test them for average level of mood. See if the smoker experiences more daily pleasure than the non-smoker. Perhaps though the toxic effects of the cigarettes cause damage that reduces pleasure other ways. I'd expect that to be the case after enough years of smoking.

In the long run I expect to see the development of wide spectrum long lasting feel good drugs that do as nicotine does but without undesired side effects such as addiction and without a delivery mechanism such as smoke that brings along lots of toxins. One reason that some people are happier than others is that they are wired up that way due to their genes. Those who go through life generally less joyful (and not just those who are depressed) will some day have the option of getting their average pleasure level turned up by adjustment of receptor concentrations in their neurons.

Share |      Randall Parker, 2005 October 07 08:14 PM  Brain Addiction


Comments
back40 said at October 7, 2005 9:02 PM:

http://www.wired.com/news/medtech/0,1286,68712,00.html?tw=rss.TOP

"If successful, ispronicline will be at the head of a whole new class of drugs that target neuronal nicotinic receptors. The receptors, found on nerve cells in the brain, respond to two chemicals: acetylcholine, which is found naturally in the brain, and nicotine.

"They're like volume knobs for the brain," said Merouane Bencherif, Targacept's vice president of preclinical research."

Randall Parker said at October 7, 2005 9:45 PM:

back40,

If nicotine up-regulates production of acetylcholine receptors (and that seems likely given the weeks of effects) and isproniciline just binds to existing receptors then isproniciline still isn't going to be as effective.

back40 said at October 7, 2005 9:59 PM:

It's just an example, perhaps, of the types of drugs you anticipate. Many others are reportedly in development. One issue is that there are apparently several different nicotinic receptors, not all having identical effects on the brain and body. We have yet to learn which is which and how to selectively stimulate them to achieve useful changes. And it seems that it isn't yet completely understood how nicotine works.

Like you, I expect to hear more about this subject in future.

James Bowery said at October 8, 2005 6:15 AM:

I don't know how related this is but I looked around a bit for ways to increase brain metabolism (basically increase the amount of glucose being burned) and found that the popular combination of caffeine and nicotine is one of the few ways to do it.

Anecdote warning:

I tried it for a few months by adding modest levels of nicotine via Equate gum (4mg/day about) and the effects were quite pronounced -- greatly reducing the amount of caffeine crashing (which comes with acetylcholine depletion as I understand it).

In the course of doing this, it became apparent that vaso-constriction is a problem with caffeine, which may be one of the reasons caffeine causes a crash, but it is less of a problem with nicotine. Ginkgo is a vaso-dilator, which may be why it has the ability to enhance some key cognitive functions like working memory (and hence, probably enhance 'g'). After discovering that I focused less on increasing brain metabolism and more on cerebral perfusion. As an experiment, I've kicked caffeine (and also cut out alcohol completely due to its tendency to reduce perfusion) so I could get a better idea of what ginkgo and some other perfusion enhancers like vinpocetine do. I still have maybe 4 to 8 mg of nicotine a week. The effects aren't profound but my vigilance level is more consistent. In a pinch for performance/vigilance I'd probably still opt for the caffeine-nicotine combination but definitely treat it as though I were taking an opiate for the flu.

Caffeine is the I don't know how related this is but I looked around a bit for ways to increase brain metabolism (basically increase the amount of glucose being burned) and found that the popular combination of caffeine and nicotine is one of the few ways to do it.

Anecdote warning:

I tried it for a few months by adding modest levels of nicotine via Equate gum (4mg/day about) and the effects were quite pronounced -- greatly reducing the amount of caffeine crashing (which comes with acetylcholine depletion as I understand it).

In the course of doing this, it became apparent that vaso-constriction is a problem with caffeine, which may be one of the reasons caffeine causes a crash, but it is less of a problem with nicotine. Ginkgo is a vaso-dilator, which may be why it has the ability to enhance some key cognitive functions like working memory (and hence, probably enhance 'g'). After discovering that I focused less on increasing brain metabolism and more on cerebral perfusion. As an experiment, I've kicked caffeine (and also cut out alcohol completely due to its tendency to reduce perfusion) so I could get a better idea of what ginkgo and some other perfusion enhancers like vinpocetine do. I still have maybe 4 to 8 mg of nicotine a week. The effects aren't profound but my vigilance level is more consistent.
In a pinch for short-term vigilance I'd probably opt for caffeine+nicotine and treat caffeine as more addictive than nicotine.

PS: Caffeine withdrawl was a real challenge -- it took over a week of lethargy and low performance. Creatine seemed to reduce the headache/lethargy.

James Bowery said at October 8, 2005 6:18 AM:

I'm not sure which key I pressed to cause that duplication. Maybe I need to consider going back on caffeine+nicotine for these early morning posts.

Marvin said at October 8, 2005 8:33 AM:

This is certainly great news for those with pet rats. Including nicotine in their feed once every week or so will enhance their appreciation of rewards. It may also make them more trainable.

David said at July 13, 2009 11:24 AM:

Nicotene is not an additon...I smoked for over 40 years and quit in 3 days....Smoking is just a bad habit like any other bad habit...This addition crap is just that..Crap....Next thing we'll be told is that eating a bowl of ice cream before bedtime is additing...Such nonsense!....Suck it up and quit if you want to.

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