Nicotine changes brain the same as other drugs

Nicotine changes brain the same as other drugs

John (Gold)
Joined: 18 Dec 2008, 23:57

28 Sep 2006, 20:30 #1

Smoking changes brain
the same way as drugs: study
Reuters, Tuesday, February 20, 2007
WASHINGTON (Reuters) - Smoking causes long-lasting changes in the brain similar to changes seen in animals when they are given cocaine, heroin and other addictive drugs, U.S. researchers said on Tuesday.

A study of the brain tissue of smokers and nonsmokers who had died showed that smokers had the changes, even if they had quit years before, the team at the National Institute on Drug Abuse reported.

"The data show that there are long-lasting chemical changes in the brains of humans," said Michael Kuhar of Emory University in Atlanta, who was not involved in the study.

"The chemical changes alone suggest a physiological basis for nicotine addiction."

A team led by Bruce Hope of NIDA, one of the National Institutes of Health, analyzed levels of two enzymes found inside brain cells known as neurons.

These enzymes help the neurons use chemical signals such as those made by the message-carrying compound dopamine.

Smokers and former smokers had high levels of these enzymes, the researchers reported in the Journal of Neuroscience.

Hope said other studies had seen the same thing in animals given cocaine and heroin -- and it was clear that the drugs were causing the effects.

"This strongly suggests that the similar changes observed in smokers and former smokers contributed to their addiction," he added in a statement.

Experts on smoking have long said that nicotine is at least as addictive as heroin.

The U.S. Centers for Disease Control and Prevention estimates that 20.9 percent of all adults smoke in the United States, which adds up to 45 million people. And 23 percent of high school students smoke.
Source link:
http://today.reuters.com/...l&src=nl_ushealth1100

© Reuters 2007. All Rights Reserved.
Last edited by John (Gold) on 17 Feb 2009, 15:08, edited 1 time in total.
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John (Gold)
Joined: 18 Dec 2008, 23:57

23 Feb 2007, 04:36 #2

Brain Changes Persist
Long After Smokers Quit
Washington Post/HealthDay News - Tuesday, February 20, 2007
TUESDAY, Feb. 20 (HealthDay News) -- Smoking produces long-lasting changes in the brains of smokers and former smokers alike, a new study suggests.

For the study, which is published in the Feb. 21 issue ofThe Journal of Neuroscience, researchers from the National Institute on Drug Abuse (NIDA) examined eight samples of human brain tissue from each of three groups: long-term smokers who smoked until death, previous long-term smokers, and nonsmokers. The samples were taken from the nucleus accumbens and the ventral midbrain, two brain regions that play a part in controlling addiction-related behaviors.

All of the participants had died of causes not related to smoking.

The researchers analyzed levels of two specific enzymes found inside brain cells that have been associated with addictive-related behaviors in animals exposed to cocaine, heroin and other illicit drugs.

Levels of these enzymes were elevated in smokers and, more interestingly, former smokers, compared with nonsmokers.

According to lead author Bruce Hope, of NIDA, these findings suggest that the brain changes persist long after smoking has ceased and could contribute to future drug relapse.

"The parallel between the new study and the animal studies is important, because a causal role has been shown in animal studies between increased levels of these neuronal signaling enzymes in these brain regions and addiction-related behaviors. This strongly suggests that the similar changes observed in smokers and former smokers contributed to their addiction," Hope said in a prepared statement.

Hope pointed out that although his findings support previous research, it is not yet clear that these biochemical changes actually cause addiction-related behaviors.

More information

The National Institute on Drug Abuse has more about nicotine addiction.

SOURCE: Society for Neuroscience, news release, Feb. 20, 2007

http://www.washingtonpost.com/...


Long-Term Upregulation of Protein Kinase A and Adenylate Cyclase Levels in Human Smokers

The Journal of Neuroscience, February 21, 2007, 27(8): pages 1964-1972


Bruce T. Hope, Deepti Nagarkar, Sherry Leonard, and Roy A. Wise

Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224, and 2Department of Psychiatry, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado 80045

Repeated injections of cocaine and morphine in laboratory rats cause a variety of molecular neuroadaptations in the cAMP signaling pathway in nucleus accumbens and ventral tegmental area. Here we report similar neuroadaptations in postmortem tissue from the brains of human smokers and former smokers. Activity levels of two major components of cAMP signaling, cAMP-dependent protein kinase A (PKA) and adenylate cyclase, were abnormally elevated in nucleus accumbens of smokers and in ventral midbrain dopaminergic region of both smokers and former smokers.
Protein levels of the catalytic subunit of PKA were correspondingly higher in the ventral midbrain dopaminergic region of both smokers and former smokers. Protein levels of other candidate neuroadaptations, including glutamate receptor subunits, tyrosine hydroxylase, and other protein kinases, were within normal range.
These findings extend our understanding of addiction-related neuroadaptations of cAMP signaling to tobacco smoking in human subjects and suggest that smoking-induced brain neuroadaptations can persist for significant periods in former smokers.

Key words: cAMP; nicotine; nucleus accumbens; addiction; neuroadaptations; PKA

Received Aug. 23, 2006; revised Jan. 12, 2007; accepted Jan. 18, 2007.

Correspondence should be addressed to Dr. Bruce T. Hope, The National Institute on Drug Abuse, Behavioral Neuroscience Branch, 5500 Nathan Shock Drive, Building C, Baltimore, MD 21224. Email: [url=mailto:bhope@intra.nida.nih.gov]bhope@intra.nida.nih.gov[/url]
Copyright © 2007 by Society for Neuroscience[/size]
Last edited by John (Gold) on 17 Feb 2009, 15:09, edited 1 time in total.
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John (Gold)
Joined: 18 Dec 2008, 23:57

23 Apr 2008, 21:05 #3

Presynaptic opioid and nicotinic receptor modulation of dopamine overflow in the nucleus accumbens.
"The Journal of Neuroscience February 2008, Volume13;28(7), Pages 1672-1681.
Britt JP, McGehee DS. Committee on Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
Behaviorally relevant stimuli prompt midbrain dopamine (DA) neurons to switch from tonic to burst firing patterns. Similar shifts to burst activity are thought to contribute to the addictive effects of opiates and nicotine. The nucleus accumbens DA overflow produced by these drugs is a key element in their pathological effects.
Using electrochemical techniques in brain slices, we explored the effects of opioids on single-spike and burst stimuli-evoked DA overflow in the dorsal and ventral striatum.
In specific subregions of the nucleus accumbens, mu-opioids inhibit DA overflow elicited with single-spike stimuli while leaving that produced by burst stimuli unaffected. This is similar to published effects of nicotinic receptor blockade or desensitization, and is mediated by opioid receptor-induced inhibition of cholinergic interneurons. Whereas delta-opioids have similar effects, kappa-opioids inhibit evoked DA overflow throughout the striatum in a manner that is not overcome with high-frequency stimuli.
These observations reveal remarkable mechanistic overlap between the effects of nicotine and opiates within the dopamine reward pathway.
PMID: 18272687 [PubMed - indexed for MEDLINE]

Source link: http://www.ncbi.nlm.nih.gov/pubmed/18272687
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John (Gold)
Joined: 18 Dec 2008, 23:57

22 May 2008, 19:36 #4


Image

Why Lapse =  Relapse

Nicotine will arrive at the brain's dopamine pathways within 8-10 seconds of that first relapse puff. Although the effects of carbon monoxide and a host of other toxins would likely have us focusing upon the fact that the act of relapse failed to match the addict's replenishment expectations still stored as memories in our brain, beneath it all, that very first puff will cause up to 50% of our brain's nicotinic-type acetylcholine receptors to be occupied by nicotine, creating a powerful dopamine surge that our brain's pay-attention pathways will find, in the short term, nearly impossible to forget.

While we would likely walk away away from the experience thinking we had gotten away with using just once, maybe not today but rest assured, the nicotine we just smoked would soon be out of our system and our brain would soon be begging for more.


We're not battling an entire pack or even a whole cigarette but just that first powerful puff. There was always only one rule ... no nicotine today!
Last edited by John (Gold) on 08 Feb 2011, 02:02, edited 1 time in total.
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FreedomNicotine
Joined: 06 Dec 2008, 16:58

17 Feb 2009, 15:06 #5

Image

The Law of Addiction
"Administration of a drug to an addict will cause reestablishment
of chemical dependence upon the addictive substance."

Smokers are often furious with me because they believe I caused them to go back to smoking. Why do they think this? Well, I have this nasty habit of making a really big deal any time a clinic participant takes one puff or maybe just a few cigarettes. The smoker feels I am so persuasive in my arguments that he has no choice but to have a full-fledged relapse. In his opinion, I forced him back to the lifetime dependency which will impair his health and may eventually cost him his life. He is convinced that if I had not made such a major issue out of the incident, he would just have smoked that one time and would never have done it again. How can I sleep each night knowing what I have done?

I sleep quite well, thank you. For, you see, I am not responsible for these people's relapses to cigarettes. They can take full credit for becoming smokers again. They relapsed because they broke the one major law of nicotine addiction - they took a puff. This is not my law. I am not setting myself up to be judge, jury, and executioner. The law of physiological addiction states that administration of a drug to an addict will cause reestablishment of the dependence on that substance. I didn't write that law. I don't execute that law. My job is much simpler than that. All I do is interpret the law. This means, by taking a puff, the smoker either goes back to full-fledged smoking or goes through the withdrawal process associated with quitting. Most don't opt for the withdrawal.

Every clinic has a number of participants who have quit in the past for one year or longer. In fact, I had one clinic participant who had stopped for a period of 24 years before he relapsed. He never heard that such a law existed, that even after 24 years, the ex-smoker is not totally freed from his imprisonment of addiction. He didn't understand that the day he tossed his "last" cigarette, he was placed "on probation" for the rest of his life. But ignorance of the law is not excusable - not the way the laws of a physiological nature are written. By the American standards of justice, this seems to be cruel and unusual punishment. But this is the way things are.

Maybe instead of going to a smoking clinic, a recently relapsed person should contact his attorney to plead his case of why he should be able to have an occasional cigarette when he desires. Maybe he can cheat just once, get a sympathetic jury, be judged innocent, and walk out of the courtroom a free and independent person. Surely, in pleading his case before twelve impartial people, he will probably have no problem convincing them that he is innocent of any wrongdoing. And, as he happily walks out of court a free and independent person, he will probably have an uncontrollable urge and then light a cigarette.

Don't look for loopholes in the law of addiction. You will be convicting yourself back to smoking. While it may seem harsh and unfair, to many, smoking is a crime punishable by death. Don't try to cheat the system - NEVER TAKE ANOTHER PUFF!


Joel

© Joel Spitzer 1988


Download your copy of "Never Take Another Puff,"
Joel's free quitting book.  Knowledge truly is power!


Last edited by FreedomNicotine on 20 Dec 2013, 14:30, edited 2 times in total.
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JohnPolito
Joined: 11 Nov 2008, 19:22

08 Feb 2011, 02:07 #6



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JohnPolito
Joined: 11 Nov 2008, 19:22

08 Feb 2011, 02:09 #7

Relative Addictiveness of Drugs
By Philip J. Hilts, New York Times, August 2, 1994

Is Nicotine Addictive? It Depends on Whose Criteria You Use.
Experts say the definition of addiction is evolving.

WASHINGTON - When heavily dependent users of cocaine are asked to compare the urge to take cocaine with the urge to smoke cigarettes, about 45 percent say the urge to smoke is as strong or stronger than that for cocaine.

Among heroin addicts, about 3 percent rank the urge to smoke as equal to or stronger than the urge to take heroin. Among those addicted to alcohol, about 50 percent say the urge to smoke is at least as strong as the urge to drink.

Yet seven chief executives of tobacco companies testified under oath before a Congressional subcommittee in April that nicotine was not addictive. Experts in addiction disagree with that assessment, but they say that the definition of addiction is evolving, and that they can see how such a statement might be made.



Hearings on Smoking This week, the Food and Drug Administration is holding hearings to consider whether cigarettes fit in the array of addictive drugs and whether the Government should regulate them.

The standard definition of addiction comes from the American Psychiatric Association and the World Health Organization, which list nine criteria for determining addiction. The two groups, which prefer the term drug dependence, base their definition on research done since the 1960's, which has determined that multiple traits must be considered in determining whether a substance is addictive. Thus although cigarettes do not offer as intense an effect as drugs like heroin and cocaine, they rank higher in a number of other factors. They not only create dependence among users but also elicit a high degree of tolerance, the need for more and more of drug to satisfy a craving. When all the factors are added up, the consensus among scientists is that nicotine is strongly addictive.

In smoking, it is not the nicotine addiction that is most harmful, but other toxic chemicals produced by burning tobacco, which cause most of the 400,000 deaths each year that are attributed to smoking.

Dr. Lynn T. Koslowski, an addiction expert at Pennsylvania State University, said addiction could generally be defined as "the repeated use of a psychoactive drug which is difficult to stop." He added that there might be many explanations for why it was hard to stop, including withdrawal that was too disturbing, or a high that was too enticing.

A diagnosis of mild dependence on a psychoactive drug is determined by meeting three of the nine criteria. Five items show moderate dependence and seven items indicate a strong dependence. (Not all nine items apply to each drug. For example, time and effort spent acquiring a drug are a significant feature of heroin addiction, but have no meaning in nicotine addiction.)



Criteria of Addiction
  1. Taking the drug more often or in larger amounts than intended.
  2. Unsuccessful attempts to quit; persistent desire, craving.
  3. Excessive time spent in drug seeking.
  4. Feeling intoxicated at inappropriate times, or feeling withdrawal symptoms from a drug at such times.
  5. Giving up other things for it.
  6. Continued use, despite knowledge of harm to oneself and others.
  7. Marked tolerance in which the amount needed to satisfy increases at first before leveling off.
  8. Characteristic withdrawal symptoms for particular drugs.
  9. Taking the drug to relieve or avoid withdrawal.
Before applying a test of the nine criteria, the expert first determines if the symptoms have persisted for at least a month or have occurred repeatedly over a longer period of time.

Asked about the tobacco executives' testimony on addiction, Dr. Kozlowski said, "In a way, I can see how they could say that. It has to do with a mistaken image of what addiction is, and I have many well-educated, intelligent people say something like that to me. People often think of a person taking one injection of heroin and becoming hopelessly addicted for the rest of their lives. That is wrong."

In addition, he said, when people tend to think of the high that heroin produces, one that is about as intense as cocaine and alcohol, they cannot believe cigarettes are in the same category. And they are not. Even though in large doses nicotine can cause a strong high and hallucinations, the doses used in cigarettes produce only a very mild high.

But researchers now know, says Dr. Jack Henningfield, chief of clinical pharmacology at the Addiction Research Center of the Government's National Institute on Drug Abuse, that many qualities are related to a drug's addictiveness, and the level of intoxication it produces may be one of the least important.

If one merely asks how much pleasure the drugs produce, as researchers used to do and tobacco companies still do, then heroin or cocaine and nicotine do not seem to be in the same category. Dr. Kozlowki said, "It's not that cigarettes are without pleasure, but the pleasure is not in the same ball park with heroin."

But now, he said, there are more questions to ask. "If the question is How hard is it to stop? then nicotine a very impressive drug," he said. "Its urges are very similar to heroin."

Among the properties of a psychoactive drug - how much craving it can cause, how severe is the withdrawal, how intense a high it brings - each addicting drug has its own profile.

Heroin has a painful. powerful withdrawal, as does alcohol. But cocaine has little or no withdrawal. On the other hand, cocaine is more habit-forming in some respects, it is more reinforcing in the scientific terminology, meaning that animals and humans will seek to use it frequently in short periods of time, even over food and water.

Drugs rank differently on the scale of how difficult they are to quit as well, with nicotine rated by most experts as the most difficult to quit.

Moreover, it is not merely the drug that determines addiction, says Dr. john R. Hughes, an addiction expert at the University of Vermont. It is also the person, and the circumstances in the person's life. A user may be able to resist dependence at one time and not at another.

A central property of addiction is the user's control over the substance. With all drugs. including heroin, many are occasional users. The addictive property of the substance can be measured by how many users maintain a casual habit and how many are persistent, regular users.

According to large Government surveys of alcohol users, only about 15 percent are regular. dependent drinkers. Among cocaine users, about 8 percent become dependent. For cigarettes, the percentage is reversed. About 90 percent of smokers are persistent daily users, and 55 percent become dependent by official American Psychiatric Association criteria, according to a study by Dr. Naomi Breslau of the Henry Ford Health Sciences Center in Detroit. Only 10 percent are occasional users.

Surveys also indicate that two-thirds to four-fifths of smokers want to quit but cannot, even after a number of attempts. Dr. John Robinson, a psychologist who works for the R. J. Reynolds Tobacco Company, contests the consensus view of nicotine as addictive. Using the current standard definition of addiction, he said at a recent meeting on nicotine addiction, he could not distinguish "crack smoking from coffee drinking, glue sniffing from jogging. heroin from carrots and cocaine from colas."

It is not that Dr. Robinson and other scientists supported by tobacco companies disagree with the main points made by mainstream scientists. but that they define addiction differently. Dr. Robinson says intoxication that is psychologically debilitating is the major defining trait of an addicting substance. It is a feature that was part of standard definitions of the 1950's, and is still linked to popular ideas about addiction, but which experts now say is too simplistic and has been left behind as scientific evidence accumulates.



Experts Rate Problem Substances Dr. Jack E. Henningfield of the National Institute on Drug Abuse and Dr. Neal L. Benowitz of the University of California at San Francisco ranked six substances based on five problem areas.
  • Withdrawal: Presence and severity of characteristic withdrawal symptoms.
  • Reinforcement: A measure of the substance's ability, in human and animal tests, to get users to take it again and again, and in preference to other substances.
  • Tolerance: How much of the substance is needed to satisfy increasing cravings for it, and the level of stable need that is eventually reached.
  • Dependence: How difficult it is for the user to quit, the relapse rate, the percentage of people who eventually become dependent, the rating users give their own need for the substance and the degree to which the substance will be used in the face of evidence that it causes harm.
  • Intoxication: Though not usually counted as a measure of addiction in itself, the level of intoxication is associated with addiction and increases the personal and socIal damage a substance may do.
1 = Most serious     6 = Least serious

HENNINGFIELD RATINGS

[/tr]
Substance
Withdrawal
Reinforcement
Tolerance
Dependence
Intoxication
Nicotine
3
4
2
1
5
Heroin
2
2
1
2
2
Cocaine
4
1
4
3
3
Alcohol
1
3
3
4
1
Caffeine
5
6
5
5
6
Marijuana
6
5
6
6
4
BENOWITZ RATINGS
Substance
Withdrawal
Reinforcement
Tolerance
Dependence
Intoxication
Nicotine
 3*
4
4
1
6
Heroin
2
2
2
2
2
Cocaine
 3*
1
1
3
3
Alcohol
1
3
4
4
1
Caffeine
4
5
3
5
5
Marijuana
5
6
5
6
4
*equal ratings
[/b]

Copyright N.Y. Times 1994, 2007
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JohnPolito
Joined: 11 Nov 2008, 19:22

07 Aug 2011, 11:06 #8

Effects of chronic nicotine on heteromeric neuronal nicotinic receptors expressed in rat primary cultured neurons.


Journal of Neurochemistry. 2011 Aug 2. doi: 10.1111/j.1471-4159.2011.07408.x. [Epub ahead of print]

Lomazzo E, Hussmann GP, Wolfe BB, Yasuda RP, Perry DC, Kellar KJ.
SourceDepartment of Pharmacology and Physiology, Georgetown University School of Medicine, Washington, DC, USA 20057 Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA 20037.

Abstract

Nicotine increases the number of neuronal nicotinic receptors (nAChRs) in brain. This study investigated the effects of chronic nicotine treatment on nAChRs expressed in primary cultured neurons. In particular, we studied the chronic Imageeffects of nicotine exposure on the total density, surface expression and turnover rate of heteromeric nAChRs. The receptor density was measured by [(125) I]epibatidine ([(125) I]EB) binding. Untreated and nicotine-treated neurons were compared from several regions of embryonic (E19) rat brain.

Twelve days of treatment with 10 μM nicotine produced a two-fold up-regulation of nAChRs. Biotinylation and whole-cell binding studies indicated that up-regulation resulted from an increase in the number of cell surface receptors as well as intracellular receptors.

nAChR subunit composition in cortical and hippocampal neurons was assessed by immunoprecipitation with subunit-selective antibodies. These neurons contain predominantly α4, β2 and α5 subunits, but α2, α3, α6 and β4 subunits were also detected. Chronic nicotine exposure yielded a two-fold increase in the β2-containing receptors and a smaller up-regulation in the α4-containing nAChRs. To explore the mechanisms of up-regulation we investigated the effects of nicotine on the receptor turnover rate. We found that the turnover rate of surface receptors was > two weeks and chronic nicotine exposure had no effect on this rate.

Journal of Neurochemistry © 2011 International Society for Neurochemistry.

PMID:21806615[PubMed - as supplied by publisher]

PubMed Link:  http://www.ncbi.nlm.nih.gov/pubmed/21806615
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