Posts tagged nicotine addiction
Articles and news from the latest research reports.
The Smoking Gun: Fish Brains and Nicotine
In researching neural pathways, it helps to establish an analogous relationship between a region of the human brain and the brains of more-easily studied animal species. New work from a team led by Carnegie’s Marnie Halpern hones in on one particular region of the zebrafish brain that could help us understand the circuitry underlying nicotine addiction. It is published the week of December 9 by Proceedings of the National Academy of Sciences.
The mammalian habenular nuclei, in a little-understood and difficult-to-access part of the brain, are involved in regulating both dopamine and serotonin, two neurotransmitters involved in motor control, mood, learning, and addiction. But unlike the mammalian habenulae, the habenular nuclei of fish are located dorsally, making them easy for scientists to access and study. However, some outstanding questions remained about the properties of the zebrafish habenulae, creating a roadblock for truly linking these structures as analogous in fish and humans. In particular, it was unresolved whether zebrafish habenular neurons produce the neurotransmitter acetylcholine, which is enriched in this region of the mammalian brain and activates the same receptors to which nicotine is known to bind.
The new work by lead author Elim Hong and colleagues confirms that the pathway between the habenula and another part of the brain called the midbrain interpenduncular nucleus utilizes acetylcholine in zebrafish, as it does in humans. The work also shows that there is a left-right difference in this part of the fish brain.
The purpose of this asymmetry is unknown, but, as demonstrated by electrophysiological recordings with collaborator Jean-Marie Mangin of the University of Pierre and Marie Curie, it results in differences in neural activity between the brain hemispheres. Other research in Halpern’s lab indicates that such left-right differences could influence behavior. Hong performed these experiments through a European Molecular Biology Organization Short-Term Fellowship while hosted in the laboratory of Claire Wyart in Paris, France.
The team further showed that this acetylcholine pathway in zebrafish responds in a similar way to nicotine as does the analagous pathway in the mammalian brain. This makes the zebrafish a good model for studying the brain chemistry of nicotine addiction.
“Our work demonstrates broader uses for zebrafish in studying the function of the habenula and addresses a major weakness in the field, which was the poor characterization of neurotransmitter identity in this area,” said Hong. “Going forward, these results will help us study how brain circuitry influences nicotine addiction.”
Heavy smokers could be helped to kick the habit by having their brains zapped with electromagnetic pulses, new research suggests.
Repeated use of a high frequency magnet to stimulate the brain helps some smokers quit for up to six months after treatment, an Israeli study found.
The smokers had already tried a range of treatments, from patches to psychotherapy, raising hopes that brain stimulation could be an effective alternative for those who had so far failed to kick the habit.
Abraham Zangen of Ben Gurion University told the annual meeting of the Society for Neuroscience in San Diego, California, that more than half the smokers given high-frequency magnetic pulses quit.
More than a third were still abstaining six months on.
'Our research shows us that we may actually be able to undo some of the changes to the brain caused by chronic smoking,' said Dr Zangen.
'We know that many smokers want to quit or smoke less and this could help put a dent in the number one cause of preventable deaths.'
Dr Zangen’s team recruited 115 heavy smokers aged between 21 and 70 who were interested in quitting but who had failed in doing so on at least two previous attempts.
They then split the smokers into three groups, giving them either high frequency repeated Transcranial Magnetic Stimulation (rTMS), low frequency rTMS, or placebo treatment for 13 days.
Repeated high frequency Transcranial Magnetic Stimulation (rTMS) is a non-invasive technique that uses magnetic fields to stimulate large areas of neurons in the brain.
The researchers focused on stimulating the prefrontal cortex and the insula, which are the two brain areas associated with nicotine addiction.
Before each session, Dr Zangen got one of his PhD students to light a cigarette and take a drag in front of half the smokers in each group to awaken their cravings.
This was to make sure the smokers’ attention was directed at their addiction and not some other craving, said Dr Zangen.
The results were striking. Nearly half - 44 per cent - of the smokers who received the cue before their rTMS session gave up immediately after the 13-day course, with 33 per cent still of the smokes six months later.
Overall, participants who received high frequency rTMS smoked less and were more likely to quit, with success rates four times that of the low frequency group and more than six times greater than the placebo group.
Dr Zangen’s team are now planning a much larger trial involving smokers in several countries, which is set to start in the next few months.
He told The Guardian: ‘It’s quite easy to quit for a few days, or even for a few weeks, but if we can help people quit for more than three months, then they are actually quite unlikely to relapse later on.’
Dr Zanger did reveal that he has a financial interest in the company which provided the Transcranial Magnetic Stimulation equipment used in the study.
Research attributes high rates of smoking among mentally ill to addiction vulnerability
People with mental illness smoke at much higher rates than the overall population. But the popular belief that they are self-medicating is most likely wrong, according to researchers at the Indiana University School of Medicine. Instead, they report, research indicates that psychiatric disease makes the brain more susceptible to addiction.
As smoking rates in the general population have fallen below 25 percent, smoking among the mentally ill has remained pervasive, encompassing an estimated half of all cigarettes sold. Despite the well-known health dangers of tobacco consumption, smoking among the mentally ill has long been widely viewed as “self-medication,” reducing the incentive among health care professionals to encourage such patients to quit.
"This is really a devastating problem for people with mental illness because of the broad health consequences of nicotine addiction," said R. Andrew Chambers, M.D., associate professor of psychiatry at the IU School of Medicine. "Nicotine addiction is the number one cause of premature illness and death in the United States, and most of that morbidity and mortality is concentrated in people with mental illness."
In a report published recently in the journal Addiction Biology, the research team lead by Dr. Chambers reported the results of experiments using an established animal model of schizophrenia in which rats display a neuropsychiatric syndrome that closely resembles the disease.
Both the schizophrenia-model rats and normal rats were given access to intravenous self-administration of nicotine.
"The mentally ill rats acquired nicotine use faster and consumed more nicotine," Dr. Chambers said. "Then when we cut them off from access to nicotine, they worked much harder to restore access to nicotine than did the normal ‘control’ rats."
In additional testing, the researchers found that administration of nicotine provided equal, but minimal, cognitive benefits to both groups of rats when performing a memory test. When the nicotine was withdrawn, however, both groups of rats were more cognitively impaired, so that any cognitive benefits to nicotine administration were “paid for” by cognitive impairments later.
“These results strongly suggest that what has changed in mental illness to cause smoking at such high rates results in a co-morbid addiction to which the mentally ill are highly biologically vulnerable. The evidence suggests that the vulnerability is an involuntary biological result of the way the brain is designed and how it develops after birth, rather than it being about a rational choice to use nicotine as a medicine,” Dr. Chambers said.
The data, he said, point to neuro-developmental mechanisms that increase the risk of addiction. Better understanding of those mechanisms could lead to better prevention and treatment strategies, especially among mentally ill smokers, Dr. Chambers said.
A video interview of Dr. Chambers discussing his research is available here.
(Source: news.medicine.iu.edu)
NIH launches neurological drug development projects
New projects will target Fragile X syndrome, nicotine addiction, and age-related macular degeneration
The National Institutes of Health has launched three innovative projects that will focus on development of therapeutics for Fragile X syndrome, nicotine addiction, and age-related macular degeneration (AMD). These projects are funded through the NIH Blueprint Neurotherapeutics Network which provides access to a variety of drug development resources.
“We are excited about the opportunity to apply cutting-edge science to the pursuit of novel treatments for these debilitating disorders” said Rebecca Farkas, Ph.D., program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS), Office of Translational Research.
The purpose of the NIH Blueprint is to provide in-depth research capabilities to increase the success rate of innovative drug discovery efforts. The program uses a virtual pharma model to provide researchers with access to support and resources that have been traditionally available to large pharmaceutical companies.
Partnerships between NIH program staff and awarded research teams are designed to bridge the funding gap between ground-breaking laboratory research and industry adoption. NIH staff helps investigators work with veteran industry drug development consultants and contract research organization capabilities from the discovery stage through preliminary clinical trials. In addition, each investigator maintains sole ownership of intellectual property associated with his or her project
NIH launched the Blueprint Neurotherapeutics Network in 2011. Including these three awards, 14 drug discovery programs have been funded as part of the program and 10 are currently active (see: http://neuroscienceblueprint.nih.gov/bpdrugs/bpn.htm).
The newly-funded investigators and their organizations are:
- Sage Therapeutics, Cambridge, Mass.
Principal Investigator: Al Robichaud, Ph.D.
Disorder: Fragile X syndrome
Project Summary: Fragile X syndrome is a genetic disorder linked to a range of neurodevelopmental disorders including learning disabilities and cognitive impairment. Many patients experience general and social anxiety yet benzodiazepines, which are drugs typically used to treat anxiety disorders, provide little relief. Their anxiety has been linked to reduced activity in the brain by a protein called, the GABA A receptor. Sage Therapeutics is developing positive allosteric modulators, designed to enhance the receptor’s activity and possibly relieve the anxiety.
- The Scripps Research Institute, Jupiter, Fla.
Principal Investigator: Paul J. Kenny, Ph.D.
Disorder: nicotine addiction
Project Summary: Nicotine addiction has been attributed to the stimulatory effects of nicotine binding to brain proteins called orexin 1 receptors. Dr. Kenny and colleagues will develop selective receptor antagonists as potential smoking cessation aids to treat people who have attempted to quit smoking but faced high relapse rates and significant side effects.
- University of Utah, Salt Lake City
Principal Investigator: Dean Yaw Li, Ph.D.
Disorder: age-related macular degeneration
Project Summary: Age-related macular degeneration is a leading cause of blindness in the United States. One form, called wet AMD, is associated with inflammation and blood vessel leakage in the retina, the eye’s light-sensitive tissue. Dean Li and his colleagues are developing small molecules that inhibit the activity of Arf6, a molecule known to help control inflammation and blood vessel leakage. This novel approach may lead to effective therapies for treating patients who do not respond to current wet AMD therapies.
(Source: nih.gov)
A Fresh Look at Psychiatric Drugs
For several years, Henry Lester, Bren Professor of Biology at Caltech, and his colleagues have worked to understand nicotine addiction by repeatedly exposing nerve cells to the drug and studying the effects. At first glance, it’s a simple story: nicotine binds to, and activates, specific nicotine receptors on the surface of nerve cells within a few seconds of being inhaled. But nicotine addiction develops over weeks or months; and so the Caltech team wanted to know what changes in the nerve cell during that time, hidden from view.
The story that developed is that nicotine infiltrates deep into the cell, entering a protein-making structure called the endoplasmic reticulum and increasing its output of the same nicotine receptors. These receptors then travel to the cell’s surface. In other words, nicotine acts “inside out,” directing actions that ultimately fuel and support the body’s addiction to nicotine.
"That nicotine works ‘inside out’ was a surprise a few years ago," says Lester. "We originally thought that nicotine acted only from the outside in, and that a cascade of effects trickled down to the endoplasmic reticulum and the cell’s nucleus, slowly changing their function."
In a new research review paper, published in Biological Psychiatry, Lester—along with senior research fellow Julie M. Miwa and postdoctoral scholar Rahul Srinivasan—proposes that psychiatric medications may work in the same “inside-out” fashion—and that this process explains how it takes weeks rather than hours or days for patients to feel the full effect of such drugs.
"We’ve known what happens within minutes and hours after a person takes Prozac, for example," explains Lester. "The drug binds to serotonin uptake proteins on the cell surface, and prevents the neurotransmitter serotonin from being reabsorbed by the cell. That’s why we call Prozac a selective serotonin reuptake inhibitor, or SSRI." While the new hypothesis preserves that idea, it also presents several arguments for the idea that the drugs also enter into the bodies of the nerve cells themselves.