Healthcare Prof:

4.33 (3 votes)

Individual brain chemistry and genes could be key to understanding why some folks become addicted to nicotine and why the chemical compound’s effects appear to diminish at night, University of Colorado at Boulder researchers say.

“The depth of a person’s addiction to nicotine appears to depend on his or her unique internal chemistry and genetic make-up,” said lead author Jerry Stitzel, an assistant professor in CU-Boulder’s department of integrative physiology and researcher with CU-Boulder’s Institute for Behavioral Genetics.

Stitzel presented his team’s findings in San Diego at Neuroscience 2007, an annual scientific meeting which is taking location Monday through Wednesday.

He and his team set out to evaluate the effects of nicotine over the course of a day by examining mice that could make and “recognize” melatonin, a powerful hormone and antioxidant, and others that could not. Scientists believe that melatonin, which is produced by darkness, tells our bodies when to sleep.

The CU researchers located that the reduced effects of nicotine at night had been dependent on the mice’s genetic make-up and regardless of whether their brains and bodies were able to recognize melatonin. They also found that the daytime effects of nicotine had been greatest when levels of the stress hormone corticosterone were high.

The second finding could explain why many smokers report that the first cigarette of the day will be the most satisfying. Cortisol, the human equivalent of corticosterone, is at peak levels in the early morning, Stitzel said.

“The negative wellness consequences of smoking have become properly known, along with a large majority of smokers say that they would like to quit,” Stitzel said. “As such, we require to understand the interaction between smoking, genes and internal chemistry so we can target new therapies to those who have a hard time quitting.”

While the team’s analysis could shed light on why men and women smoke and how nicotine affects them, Stitzel says more research is required to determine the role that melatonin plays in altering the effects of nicotine, and whether or not the correlation in between greater corticosterone levels and nicotine sensitivity can be a coincidence.

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The CU-Boulder study was funded by the National Institute on Drug Abuse, a part of the National Institutes of Wellness.

Researchers from Yale, Florida State, the University of Minnesota and the Baylor College of Medicine also presented findings according to research into the effects of smoking and nicotine.

Among their conclusions: Smoking may possibly predispose adolescents to mental disorders in adolescence and adulthood; a network of neurons, or cells within the nervous system, may possibly regulate the body’s craving response; and smoking could affect decision-making.

For a lot more information concerning the CU-Boulder department of integrative physiology and the Institute for Behavioral Genetics, visit http://www.colorado.edu/intphys// and http://ibgwww.colorado.edu/.

Source: Jerry Stitzel
University of Colorado at Boulder

four.5 (2 votes)

Healthcare Prof:

Bupropion in combination with counseling seems to aid teenagers give up smoking more successfully inside the short term, according to an post in Archives of Pediatrics & Adolescent Medicine (JAMA/Archives).

Approximately 1 quarter of all American high school students are cigarette smokers, the authors explain. A large number of teenage smokers would like to give up. Even so, based on recent studies, only approximately 4% manage to successfully quite each year. Bupropion, an antidepressant drug, has been shown to assist adults give up smoking. Bupropion is also employed to treat attention deficit disorders in kids.

Myra L. Muramoto, M.D., M.P.H., Scott J. Leischow, Ph.D., University of Arizona, Tucson, and team carried out a clinical trial with 312 teenagers aged 14-17. They all smoked no less than six cigarettes per day and had tried to give up at least twice. They were randomly selected to receive 105 teens (150 milligrams) or 104 teens (300 milligrams) of bupropion, or a placebo (103 teens). They all visited the clinic once a week for a total of seven weeks – six weeks included therapy plus 1 week post-treatment. They also attended individual cessation counseling sessions lasting ten to 20 minutes each. They had been followed-up by telephone soon after 12 weeks, and then again face-to-face right after 26 weeks.

The 300-milligram group had greater quit rates than the placebo group for every week, except for week four. 5.6% continued not to smoke right after six weeks from the placebo group, compared to 10.7% in the 150-milligram bupropion group and 14.5% within the 300-milligram bupropion group.

At 26 weeks the quit rate among the 300-milligram group was considerably greater than the placebo group and the 150 millgram group. The researchers checked quit rates by measuring the level of cotinine in the participants’ urine. Cotinine is really a byproduct of nicotine.

The authors noted that even though those on 300 milligrams of bupropion had a better quit rate than those in the other groups, adults on 300 milligrams of bupropion have a substantially higher quit rate. It’s probable that younger smokers may need a longer therapy period.

The authors conclude “Nonetheless, this study provides hope for helping a generation of smokers quit prior to they become adults. These outcomes are critically essential due to the fact few efficient remedy options are available for adolescent smokers who want to quit.”

“Randomized, Double-blind, Placebo-Controlled Trial of 2 Dosages of Sustained-Release Bupropion for Adolescent Smoking Cessation”
Myra L. Muramoto, MD, MPH; Scott J. Leischow, PhD; Duane Sherrill, PhD; Eva Matthews, MPH; Louise J. Strayer, BSc, RN, MSc
Arch Pediatr Adolesc Med. 2007;161(11):1068-1074.
Click here to view abstract online

Written by – Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Nowadays

Healthcare Prof:

1.67 (3 votes)

The interaction in between nicotine and alcohol, two of one of the most abused and co-abused drugs, can impact a person’s ability to learn and could have implications for treating addiction, based on researchers at Temple University.

The researchers, Thomas J. Gould and Danielle Gulick, presented their findings, “Acute, chronic, and withdrawal from chronic nicotine interacts with acute ethanol to modulate fear conditioning,” in the annual meeting of the Society for Neuroscience in San Diego. The study has also been accepted for publication inside the peer-reviewed journal, Psychopharmacology.

“Whenever someone uses these two drugs together, there must be a reason why,” says Gould, an associate professor of psychology at Temple. “The goal of our analysis is always to fully grasp the interactive effects of these two drugs and, by understanding how they are altering behavior and producing neural adjustments, we will hopefully be in a much better position to develop treatments for drug addiction.”

In examining the drugs’ interactive effects on learning, the researchers looked in the ability to learn and process contextual data, which is important for multiple reasons. Based on Gould, contextual learning taps into the part of the brain which is involved in declarative memory processes that define who we are, including memories of our family, our wedding day, or graduating from school. This type of learning involves an region of the brain called the hippocampus, an area that’s involved in strengthening short-term memories, and putting them into long-term memory storage, therefore creating those memories the ones that define who we are.

“We wanted to see if nicotine and alcohol are interacting within the hippocampus, or at another level, and what processes inside the brain are they interacting with,” Gould says. “If we can understand how these neural processes are changing and how they interact, then when someone is going through withdrawal or experiencing a cognitive deficit because of one of these two substances, we then may possibly be able to use a therapeutic that blocks or activates a receptor, or that blocks a particular pathway which prevents the occurrence of the withdrawal symptoms and falling back into relapse.”

Using an animal model, Gould and Gulick examined the effects of alcohol and nicotine on learning to determine what takes place as the drugs are combined at different doses and different stages of administration.

“Our study showed that initially nicotine in a dose-dependent manner reverses alcohol-induced deficits in learning, but tolerance develops for this effect of nicotine with continued administration,” he says. “We also found that a low dose of alcohol reverses nicotine withdrawal-associated deficits in learning. Furthermore, we discovered that chronic nicotine produces cross-tolerance towards the effects of a low dose of alcohol on learning.”

What does this all mean in terms of addiction?

“Think of a situation in which somebody is drinking and having cognitive difficulties,” says Gould. “Smoking might take the edge off of it at first, so they begin smoking and they smoke much more and far more until tolerance develops and they lose that edge.

“Now they are drinking and smoking and they are addicted to each,” he adds. “But if they try to quit smoking, they go into nicotine withdrawal, which results in a learning deficit. Maybe a drink will actually aid them out initially, but then they consume a lot more and they develop even worse learning deficits, so now they begin smoking again and they end up relapsing.”

According to Gould, this could feed into a spiral in which initially nicotine and alcohol each block the adverse effects of the other. But as that takes place, he says, smokers and drinkers develop tolerance and consume greater amounts of every drug, and then when they try quitting 1 or the other, they then have this cognitive deficit and may possibly reach for either alcohol or nicotine or each to try and reverse it, but they just spiral into the addiction again.

###

This study was funded by the National Institute on Alcoholism and Alcohol Abuse (NIAAA) and the National Institute on Drug Abuse (NIDA).

Source: Preston M. Moretz
Temple University

5 (three votes)

Healthcare Prof:

5 (1 votes)

The interaction between nicotine and alcohol, two of probably the most abused and co abused drugs, can impact a person’s ability to learn and could have implications for treating addiction, in accordance with researchers at Temple University.

The researchers, Thomas J. Gould and Danielle Gulick, will present their findings, “Acute, chronic, and withdrawal from chronic nicotine interacts with acute ethanol to modulate fear conditioning,” on Nov. 6 in the annual meeting of the Society for Neuroscience in San Diego. The study has also been accepted for publication within the peer-reviewed journal, Psychopharmacology.

“Whenever someone uses these two drugs together, there must be a reason why,” says Gould, an associate professor of psychology at Temple. “The goal of our investigation would be to realize the interactive effects of these two drugs and, by understanding how they are altering behavior and producing neural adjustments, we will hopefully be in a far better position to develop treatments for drug addiction.”

In examining the drugs’ interactive effects on learning, the researchers looked at the ability to learn and process contextual information, that is critical for multiple reasons. According to Gould, contextual learning taps into the part of the brain which is involved in declarative memory processes that define who we are, such as memories of our family, our wedding day, or graduating from school. This type of learning involves an region of the brain known as the hippocampus, an area that is involved in strengthening short-term memories, and putting them into long-term memory storage, thus creating those memories the ones that define who we are.

“We wanted to see if nicotine and alcohol are interacting within the hippocampus, or at another level, and what processes inside the brain are they interacting with,” Gould says. “If we can understand how these neural processes are changing and how they interact, then when someone is going through withdrawal or experiencing a cognitive deficit since of 1 of these two substances, we then could be able to use a therapeutic that blocks or activates a receptor, or that blocks a particular pathway which prevents the occurrence of the withdrawal symptoms and falling back into relapse.”

Using an animal model, Gould and Gulick examined the effects of alcohol and nicotine on learning to determine what happens as the drugs are combined at different doses and different stages of administration.

“Our study showed that initially nicotine in a dose-dependent manner reverses alcohol-induced deficits in learning, but tolerance develops for this effect of nicotine with continued administration,” he says. “We also identified that a low dose of alcohol reverses nicotine withdrawal-associated deficits in learning. Furthermore, we discovered that chronic nicotine produces cross-tolerance to the effects of a low dose of alcohol on learning.”

What does this all mean in terms of addiction?

“Think of a situation in which somebody is drinking and having cognitive difficulties,” says Gould. “Smoking might take the edge off of it at 1st, so they begin smoking and they smoke a lot more and a lot more until tolerance develops and they lose that edge.

“Now they are drinking and smoking and they are addicted to both,” he adds. “But if they try to quit smoking, they go into nicotine withdrawal, which outcomes in a learning deficit. Maybe a drink will actually assist them out initially, but then they consume much more and they develop even worse learning deficits, so now they begin smoking again and they end up relapsing.”

According to Gould, this could feed into a spiral in which initially nicotine and alcohol every block the adverse effects of the other. But as that occurs, he says, smokers and drinkers develop tolerance and consume greater amounts of each drug, and then when they try quitting one or the other, they then have this cognitive deficit and might reach for either alcohol or nicotine or both to try and reverse it, but they just spiral into the addiction again.

This study was funded by the National Institute on Alcoholism and Alcohol Abuse (NIAAA) and the National Institute on Drug Abuse (NIDA).

Temple University
301 University Services Bldg.1601 North Broad St.
Philadelphia, PA 19122
United States
http://www.temple.edu

Healthcare Prof:

5 (1 votes)

Researchers have uncovered a key genetic switch that chronic cocaine or stress influences to trigger the brain to descend into a pathological state. In research with mice they showed how chronic cocaine modifications gene activity to enhance the addictive reward from the drug. And they showed similarly how chronic stress induces the same kinds of changes that hypersensitizes the brain, causing depression-like symptoms.

The researchers said their basic finding inside the animals could lead to better treatments for addiction, depression and other psychiatric disorders.

Eric Nestler and colleagues published their findings within the November 8, 2007, concern of the journal Neuron, published by Cell Press.

In their experiments, the researchers explored how chronic cocaine or stress exerts “epigenetic” control of genes within the brain. Such control involves repressing or activating genes by altering the structure of the chromatin that enwraps genes. Specifically, the researchers explored whether chronic cocaine or stress have an effect on an enzyme referred to as histone deacetylase 5 (HDAC5). Usually, HDAC5 represses specific genes by removing molecules known as acetyl groups from the histone proteins that make up the chromatin surrounding them. The researchers’ prior research had shown that chronic cocaine administration in mice caused an enhance in acetyl groups in a brain region referred to as the nucleus accumbens (NAc), known to be involved in response to cocaine or stress.

The researchers’ studies showed that giving mice chronic cocaine led to a reduction in HDAC5, allowing some 172 genes to be activated. What’s more, they identified that this loss of HDAC5 inside the NAc created the mice a lot more sensitive towards the reward of chronic cocaine. They determined the animals’ reward-sensitivity to cocaine by measuring the mice’s preference for an location of a box that they were taught to associate with receiving cocaine.

The researchers also studied no matter whether the animals’ adaptation to chronic stress involved HDAC5 levels. In these experiments, they exposed mice to aggressive mice and measured the resulting depressive behavior. The researchers found that such stress also reduced HDAC5 function, despite the fact that through a different mechanism than for chronic cocaine.

“These data demonstrate a crucial role for HDAC5 in regulating behavioral adaptations to chronic stress in addition to chronic cocaine and recommend that HDAC5 contributes to a molecular switch among acute stress responses and much more long-lasting depression-like maladaptations,” wrote the researchers.

“The functions of HDAC5 described here provide new insight into the pathogenesis of drug addiction, depression, and other stress-related syndromes,” they wrote. “This fundamentally new insight into the molecular underpinnings of chronic maladaptation in brain could lead to the development of improved treatments for addiction, depression, and other chronic psychiatric disorders.”

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The researchers include Eric J. Nestler,William Renthal, Ian Maze, Vaishnav Krishnan, Herbert E. Covington, III, Arvind Kumar, Rhonda Bassel-Duby, Eric N. Olson, Scott J. Russo, Ami Graham, Nadia Tsankova, Guanghua Xiao, of the The University of Texas Southwestern Medical Center, Dallas, TX. USA; Tod E. Kippin, and Kerry A. Kerstetter, of the Department of Psychology, University of California, Santa Barbara, Santa Barbara, CA, USA; Rachael L. Neve, of Harvard Medical School and McLean Hospital, in Belmont, MA, USA; Stephen J. Haggarty, of the Department of Chemistry and Chemical Biology, Harvard University, in Cambridge, MA, USA; and Timothy A. McKinsey, of Myogen, Inc./Gilead Colorado, Inc.,Westminster, CO, USA.

Source: Cathleen Genova
Cell Press

4 (1 votes)

Healthcare Prof:

3.67 (three votes)

Article Opinions:1 posts
New measurements of brain activity in people addicted to cocaine confirm that addicted people have compromised sensitivity to monetary rewards.

“This altered sensitivity to reward could assist explain why some drug-addicted people are unable to modify their drug-taking behavior, even inside the face of well-understood negative consequences and/or positive incentives for behavioral change,” said Rita Goldstein, who runs the neuropsychoimaging lab at the U.S. Department of Energy’s Brookhaven National Laboratory where the work was done. Muhammad A. Parvaz, a Stony Brook University graduate student working with Goldstein, presented the findings in the Society for Neuroscience annual meeting in San Diego on November 7, 2007.

The researchers studied 18 current cocaine users and 18 age-matched control subjects. They outfitted each and every subject having a cap of electrodes to measure brain activity soon after instructing the subjects to press or not press a button in response to certain visual prompts. Throughout the task, subjects were told they could earn various amounts of money for fast and accurate performance.

The scientists had been specifically interested in the P300 component of the brain waves “time locked” to the task (known as Event-Related Potentials). The P300, a positive voltage potential occurring at a latency of 300 milliseconds after presentation of a novel or meaningful stimulus, has been shown to be blunted in individuals addicted to alcohol and their offspring. The present study demonstrates, for the initial time, a blunted P300 response to a commonly occurring and generalized abstract reward — money — in cocaine-addicted people with recent cocaine use.

The findings: In healthy control subjects, the P300 response was substantially greater and both accuracy and speed of efficiency had been considerably much better and faster, respectively, when a monetary reward was offered compared with when the reward was absent (45 vs. 0 cents). These responses to money in both brain and behavioral measures — and their interdependence — were decreased in cocaine-addicted people. In addition, those who had used cocaine most frequently during the year preceding the study had been the least able to improve their behavioral performance in response to monetary rewards.

Interestingly, these outcomes could not be attributed to decreased task engagement inside the cocaine users, who instead reported being far more interested inside the task than the control subjects. It’s possible that this heightened interest could be attributed to recent cocaine use, which was documented in all cocaine-using subjects in this study by positive urine screening tests.

“So despite greater self-reported interest, cocaine users did not respond faster or more accurately and their brain activity did not alter in response to monetary reward towards the same degree as in the healthy control subjects,” Parvaz said.

These results confirm findings from earlier studies conducted in Goldstein’s lab that utilized functional magnetic resonance imaging (fMRI) to demonstrate a similar compromise in neural sensitivity to monetary reward in cocaine addiction.

“Individuals with such blunted neural and behavioral sensitivity to rewards could have a particularly difficult time responding to abstract incentives designed to motivate behavioral modifications — especially when outside of a structured remedy environment or when rewards are not readily available or clearly contingent on behavior,” Goldstein said.

“It would be interesting to see if there are any differences among the cocaine users studied here, who were not seeking treatment, and those in remedy or abstinent for longer periods of time,” Parvaz suggested. Such a comparison would permit the researchers to determine whether recovery of sensitivity to reward can be expected, and assess the time frame for such recovery. The researchers might also extend the study to see if their findings can be generalized to negative reinforcement, such as the loss of money.

###

This analysis was funded by: the Office of Biological and Environmental Investigation (OBER) within the U.S. Department of Energy’s Office of Science; the National Institute on Drug Abuse; Laboratory Directed Study and Development funding from OBER; a Young Investigator Award from NARSAD (a mental health research association); a Stony Brook University/Brookhaven National Laboratory seed grant; the National Institute on Alcohol Abuse and Alcoholism; and by Stony Brook University’s General Clinical Study Center.

One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research within the physical, biomedical, and environmental sciences, in addition to in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE’s Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.

Source: Karen McNulty Walsh
DOE/Brookhaven National Laboratory

Healthcare Prof:

Article Opinions:3 posts
A new coalition launched these days is calling on the Government to do much more to prevent the rise in alcohol-related diseases. The Alcohol Well being Alliance UK can be a ground-breaking coalition of 24 organisations whose mission is to lessen the damage caused to well being by alcohol misuse and who will work together to:

-Highlight the rising levels of alcohol-related well being harm
-Propose evidence-based solutions to lessen this harm
-Influence decision makers to take positive action to address the damage caused by alcohol misuse

While loose coalitions have previously been formed on specific topics in the medical field, notably tobacco control, this will be the 1st time that a group has existed specifically to co-ordinate campaigning on alcohol, bringing together medical bodies, patient representatives and alcohol health campaigners. The formation of the Alliance comes at a time when:

-13 children a day are hospitalised as a result of alcohol misuse
-Alcoholic liver cirrhosis has increased by 95% since 2000, and by 36% over the last two years to 2006 and is still increasing
-Overall alcohol related deaths have increased by 18% from 2002-2005
-More folks die from alcohol related causes than from breast cancer, cervical cancer and MRSA combined
-The ‘passive effects’ of alcohol misuse are catastrophic – rape, sexual assault, domestic and other violence, drunk driving and street disorder – alcohol affects thousands much more innocent victims than passive smoking

The Alcohol Wellness Alliance UK will campaign for:

-Dedicated funding for alcohol therapy and prevention strategies
-Increased taxation on alcohol
-A ban on alcohol advertising before 9.00 pm and in cinemas apart from 18 rated films
-Promotional material to carry information on health related harm
-The drink driving limit to be reduced to the EU standard of 0.5g/l and a near zero limit for new drivers

Membership of the Alcohol Health Alliance UK

Academy of Medical Royal Colleges, Action on Addiction, Alcohol and Well being Analysis Trust, Alcohol Concern, Alcohol Education and Study Council, British Association for the Study of the Liver, British Liver Trust, British Society of Gastroenterology, College of Emergency Medicine, Faculty of Dental Surgery, Faculty of Occupational Medicine, Faculty of Public Well being, Institute of Alcohol Research, Medical Council on Alcohol, National Addiction Centre, National Organisation on Fetal Alcohol Syndrome – UK, Royal College of General Practitioners, Royal College of Nursing, Royal College of Physicians of Edinburgh, Royal College of Physicians of London, Royal College of Physicians and Surgeons of Glasgow, Royal College of Psychiatrists, Royal College of Surgeons of England, Scottish Intercollegiate Group on Alcohol/SHAAP.

Royal College of Physicians