1. Study looks at socioeconomic aspects of drinking

    May 19, 2017 by Ashley

    From the University of Washington press release:

    Neighborhoods with greater poverty and disorganization may play a greater role in problem drinking than the availability of bars and stores that sell hard liquor, a University of Washington-led study has found.

    While there is evidence for the link between neighborhood poverty and alcohol use, the new twist — that socioeconomics are more powerful environmental factors than even access to the substance itself — suggests that improving a neighborhood’s quality of life can yield a range of benefits.

    “Is there something about the neighborhood itself that can lead to problems? As we learn more about those neighborhood factors that are relevant, then this might point to population-level strategies to modify or improve the environments where people live,” said Isaac Rhew, a research assistant professor in the Department of Psychiatry & Behavioral Sciences.

    A common way to think of such broader changes is the “broken windows” theory of maintaining neighborhoods to deter crime. In other words, implementing programs, services or clean-up efforts to improve a neighborhood could help attain another goal: reducing problem drinking.

    The UW study was published online May 8 in the Journal of Urban Health.

    In examining the combination of multiple neighborhood factors on alcohol use, UW researchers turned to an ongoing research study of adults the university’s Social Development Research Group has followed for decades. They interviewed more than 500 of the adults in the study, who were first identified as fifth-graders in Seattle elementary schools and now live throughout King County. In this neighborhood study, 48 percent of participants were women; people of color made up nearly 60 percent of respondents.

    Researchers determined the U.S. Census Block Group (a geographic area of roughly 1,000 people) of each participant’s residence, along with demographic data tied to that area and the number of locations that sold hard alcohol there. Participants also answered a series of questions about their alcohol consumption and their perceptions of their neighborhood.

    This information allowed researchers to classify neighborhoods according to poverty level, alcohol availability (location of bars and liquor stores) and “disorganization,” which included factors such as crime, drug selling and graffiti.

    The ability to consider a number of neighborhood characteristics simultaneously and to identify patterns of how these characteristics grouped together to form distinct neighborhood types made this study different from others that might focus on the impact of, say, poverty alone, Rhew said.

    And while poverty and disorganization often are assumed to go hand-in-hand, that’s not always the case, added study co-author Rick Kosterman, a research scientist in the UW School of Social Work. A socioeconomically disadvantaged neighborhood might also be highly organized, with strong leaders, a sense of identity and various programs and services for residents. At the same time, a low-poverty neighborhood might be highly disorganized, with a lack of resources or sense of community, or a few streets with more trouble than others.

    In this study, researchers found that residents of neighborhoods primarily characterized by high poverty and disorganization tended to drink twice as much in a typical week as those in other types of neighborhoods. Binge-drinking — generally defined as more than four drinks at a time for women, five for men — occurred in these high-poverty, highly disorganized communities about four times as frequently as in other types of neighborhoods. These findings are consistent with previous research indicating that people in lower income neighborhoods may be at greater risk for alcohol-related problems, Rhew said.

    What’s different, Rhew and Kosterman agreed, is the fact that neighborhoods characterized by greater alcohol availability showed no increased alcohol use among residents — suggesting that socioeconomic factors may pose a greater risk for substance abuse.

    “On its face, the connection between poverty and disorganization and alcohol use may not be all that surprising, but when you find that this connection may be even more important than the location of bars and liquor stores, then it’s those characteristics of a neighborhood that we want to pay attention to,” Kosterman said.

    Researchers pointed to an important change that has occurred since their original data was collected: the passage of a state law in 2011 privatizing liquor sales. The availability of liquor went from a little more than 300 state-run stores to some 1,500 pharmacies, grocery stores and warehouse clubs.

    “Prior to privatization, locations of stores that sold hard liquor were more controlled by the state, so now a neighborhood that had one store that sold liquor could have several,” said Rhew. But the evidence is mixed in terms of the impact that nearby alcohol outlets have on alcohol use, he added. People who purchase alcohol in one location, for instance, may live in another.

    “People who utilize the outlets aren’t just people from the neighborhood. We see stronger evidence of the link between where alcohol is sold and other problems such as violence, crime, and drinking and driving, but not necessarily consumption,” he added.

    The ability, thanks to recent funding, to overlay neighborhood data with the longitudinal Seattle Social Development Project — the study of 808 individuals begun in 1985 — presents opportunities for future analyses of a variety of behaviors and circumstances, the researchers said.


  2. Study examines neuroscience of craving in addiction and binge eating

    May 11, 2017 by Ashley

    From the Center for BrainHealth press release:

    A new article in JAMA Psychiatry details the first step in revealing how craving works in the brain. Scientists at the Center for BrainHealth at The University of Texas at Dallas are the first to propose a systematic and quantitative model for drug addiction research. The model focuses on craving: the intense, urgent feeling of needing or wanting drugs. Their ongoing research and subsequent findings have the potential to open a new frontier of alcohol and substance abuse treatment that may also apply to binge-eating disorders.

    Craving is considered one of the strongest predictors of relapse,” said Dr. Xiaosi Gu, who runs the Computational Psychiatry Unit at the Center for BrainHealth. “Even after an individual has broken the cycle of compulsive drug taking, craving can still persist. Although current treatment can handle a lot of the behavioral aspects of addiction, especially physical symptoms, craving is difficult to treat because it is a subject state. For example, when you are hungry, you have the urge to eat, but it is difficult to measure how compelling your urge to eat is in a quantitative way. However, if we could visualize craving activation in the brain, we would be better able to quantify and target it. We aim, with this new framework, to begin to separate craving from reward- or drug-seeking behavior.”

    Research on drug craving has traditionally centered on studying cue response. For example, a marijuana study participant typically undergoes a brain scan while being shown a picture of a bong, and researchers analyze the brain activation in response to the cue. In this scenario, the bong is a valuable item to someone who uses marijuana. However, as Dr. Gu points out, there is no way to know whether the brain activation occurs in response to the reward (an item associated with smoking marijuana) or the craving (the bong image triggers craving for marijuana).

    Dr. Gu and Dr. Francesca Filbey, also of the Center for BrainHealth and Bert Moore Chair at BrainHealth, are collaborating to identify — using a new computational model — the exact regions of the brain that encode craving. They plan to reanalyze brain scans from previous research to lay the groundwork for quantifying craving, its effects and ways to target treatments to counteract it.

    Initial results are promising, but it will take a few years and additional funding to complete reanalysis of the thousands of brain scans previously compiled through Dr. Filbey’s research as well as data from consortia to which Dr. Filbey belongs.


  3. Study suggests standardized cigarette packaging may reduce the number of people who smoke

    May 3, 2017 by Ashley

    From the Wiley press release:

    A Cochrane Review published today finds standardized tobacco packaging may lead to a reduction in smoking prevalence and reduces the appeal of tobacco.

    According to the World Health Organization, tobacco use kills more people worldwide than any other preventable cause of death. Global health experts believe the best way to reduce tobacco use is by stopping people starting to use tobacco, and encouraging and helping existing users to stop.

    The introduction of standardized (or ‘plain’) packaging was recommended by the World Health Organisation Framework Convention on Tobacco Control (WHO FCTC) guidelines. This recommendation was based on evidence around tobacco promotion in general and studies which examined the impact of changes in packaging on knowledge, attitudes, beliefs and behaviour. Standardized tobacco packaging places restrictions on the appearance of tobacco packs so that there is a uniform colour (and in some cases shape), with no logos or branding apart from health warnings and other government-mandated information; the brand name appears in a prescribed uniform font, colour, and size.

    A number of countries have implemented, or are in the process of implementing, standardized tobacco packaging. Australia was the first country in the world to implement standardized packaging of tobacco products. The laws, which took full effect there in December 2012, also required enlarged pictorial health warnings.

    A team of Cochrane researchers from the UK and Canada have summarized results from studies that examine the impact of standardized packaging on tobacco attitudes and behaviour. They have published their findings in the Cochrane Library.

    They found 51 studies that looked at standardized packaging. The studies differed in the way they were done and also what they measured. Only one country had implemented standardized packaging at the time of this review, so evidence that tobacco use prevalence may have decreased following standardized packaging comes from one large observational study. A reduction in smoking behaviour is supported by routinely collected data from the Australian government. There are data from a range of other studies to indicate that appeal is lower with standardized packaging and this may help to explain the observed decline in prevalence. Researchers did not find any evidence suggesting that standardized packaging may increase tobacco use. No studies directly measured whether standardized packs influence uptake, cessation or whether they prevent former smokers from taking up smoking again.

    The amount of evidence for standardized packaging has increased markedly since the publication of the WHO guidelines in 2008. However, given its recency, there are no data on long-term impact. The amount of evidence will continue to expand as more countries implement standardized packaging and as studies assessing the longer-term effects of the Australian policy become available.

    Cochrane lead author, and Deputy Director of the UK Centre for Tobacco and Alcohol Studies, Professor Ann McNeill from King’s College London, said, “Evaluating the impact of standardized packaging on smoking behaviour is difficult to do; but the evidence available to us, whilst limited at this time, indicates that standardized packaging may reduce smoking prevalence. These findings are supported by evidence from a variety of other studies that have shown that standardized packaging reduces the promotional appeal of tobacco packs, in line with the regulatory objectives set. It would appear that the impact of standardized packaging may be affected by the detail of the regulations such as whether they ban descriptors, such as ‘smooth’ or ‘gold’, and control the shape of the tobacco pack.”

    Co-author Jamie Hartmann-Boyce, from the Cochrane Tobacco Addiction Group, Oxford, UK, added: “Our evidence suggests that standardized packaging can change attitudes and beliefs about smoking, and the evidence we have so far suggests that standardized packaging may reduce smoking prevalence and increase quit attempts. We didn’t find any studies on whether changing tobacco packaging affects the number of young people starting to smoke, and we look forward to further research on this topic.”


  4. Study suggests gender differences in effects of alcoholism on the brain’s reward system

    April 25, 2017 by Ashley

    From the Massachusetts General Hospital press release:

    A collaborative study between researchers at Massachusetts General Hospital (MGH) and Boston University School of Medicine (BUSM) has found evidence implying that alcoholism may have different effects on the reward system in the brains of women than it does in men.

    In their paper published in Psychiatry Research Neuroimaging, the team reports that reward system structures are larger in alcoholic women than in nonalcoholic women, and their report confirmed earlier studies that found the same structures were smaller in alcoholic men than in nonalcoholic men. The study, which enrolled currently abstinent individuals with a history of long-term alcohol use disorder, also found a negative association between the length of sobriety and the size of the fluid-filled ventricles in the center of the brain, suggesting possible recovery of the overall brain from the effects of alcoholism.

    “Until now, little has been known about the volume of the reward regions in alcoholic women, since all previous studies have been done in men,” says co-author Gordon Harris, PhD, of the 3D Imaging Service and the Center for Morphometric Analysis in the Martinos Center for Biomedical Imaging at MGH. “Our findings suggest that it might be helpful to consider gender-specific approaches to treatment for alcoholism.”

    The brain’s reward system is a group of structures – including the amygdala and the hippocampus – that reinforce beneficial experiences, are involved in memory and complex decision-making and have been implicated in the development of substance use disorders. Since there are known difference between the psychological and behavioral profiles of women and men with alcoholism – women tend toward having higher levels of anxiety, while men are more likely to exhibit anti-social characteristics – the current study was designed to investigate whether the alcoholism-associated reward system differences previously observed in men would also be seen in women.

    The study enrolled 60 participants with histories of long-term alcoholism – 30 women and 30 men – and an equivalent group of nonalcoholic volunteers. The alcoholic participants had been abstinent for time periods ranging from four weeks to 38 years. Participants completed detailed medical histories and neuropsychological assessments with the BUSM researchers before having MRI brain scans at the Martinos Center that were analyzed both in terms of the total brain and of the structures in the reward network.

    Replicating the results of earlier studies, the average sizes of reward region structures of alcoholic men were 4.1 percent smaller than those of nonalcoholic men, but the average sizes of the same structures were 4.4 percent larger in alcoholic than in nonalcoholic women. While factors such as the duration and intensity of heavy drinking appeared to reinforce these gender-specific effects, the research team notes that the current study cannot determine whether these differences preceded or resulted from the development of alcoholism. Among participants with alcoholism – both women and men – each year of sobriety was associated with a 1.8 percent decrease in the size of the ventricles, suggesting recovery from the damaging effects of alcoholism on the brain.

    “We’re planning to take a more detailed look at the impact of factors such as the severity of drinking and the length of sobriety on specific brain structure, and hope to investigate whether the imaging differences seen in this and previous studies are associated with gender-based differences in motivational and emotional functions,” says co-author Marlene Oscar-Berman, PhD, a professor of Psychiatry, Neurology, and Anatomy & Neurobiology at BUSM.


  5. Brains of gambling addicts: High stakes, high risk, and a bad bet

    April 22, 2017 by Ashley

    From the Kyoto University press release:

    You’ve been losing all night, and now another bad hand. So why raise?

    Gambling addiction is a mental disorder characterized by excessive risk-taking despite negative results. Scientific studies using functional MRI — fMRI, a method of looking at active areas of the brain — have previously shown that addicts have altered activity in brain regions related to risk and reward, making them prone to prefer risky choices.

    New fMRI research conducted at Kyoto University has now found another explanation for the unhealthy bent: addicts have a poor ability to assess and adapt to high risk situations. The study appeared recently in Translational Psychiatry.

    “We noticed that gambling addicts also have higher levels of mood and anxiety disorders,” says lead author Hidehiko Takahashi. “Hence pleasure may not be the main goal, but rather an inability to properly recognize risk and adapt accordingly.”

    We all make action decisions by evaluating the likelihood of success based on the level of tolerable risk. We then make adjustments based on prevailing circumstances.

    “For example, if you are losing in the first half of a soccer match, you will likely prefer a strong defense while pushing your attackers forward,” continues Takahashi, “However, if you are losing at the end of the second half, you may choose to forgo defense in favor of an all-out attack, because you would lose otherwise.”

    Addicts, on the other hand, are inclined toward unnecessarily risky action, demonstrating a defect in risk assessment and adaptation.

    Flexibility in risk-taking between addicts and non-addicts was determined through a series of gambling tasks, requiring participants to earn a certain amount of credits. Addicts were found to go with a risky strategy even if that choice was sub-optimal.

    “We observed diminished activity in the dorsolateral prefrontal cortex, a region of the brain involved in cognitive flexibility,” concludes Takahashi. “This indicates that these subjects lack an ability to adapt their behavior to the risk level of the situation.”

    The team hopes that their findings will contribute to a better understanding of the nature of gambling addiction, and eventually to the development of new methods of treatment.


  6. Study suggests heavy drinking impacts performance over time

    April 21, 2017 by Ashley

    From the Veterans Affairs Research Communications press release:

    Heavy drinkers develop behavioral tolerance to alcohol over time on some fine motor tasks, but not on more complex tasks, according to a study led by a Veterans Affairs San Diego Healthcare System researcher. While heavy drinkers showed less impairment than light drinkers on a rote fine motor test over time, they did not perform better on a test involving more short-term memory, motor speed, and more complex cognitive processing.

    The study offers new insight into the changes and problems that accompany excessive drinking. As the researchers explain, “The results have implications for our understanding of alcohol-induced impairments across neurobehavioral processes in heavy drinkers and their ongoing risks for alcohol-related consequences over time.”

    Lead researcher Dr. Ty Brumback adds, “The most important thing about the study is that despite heavy drinkers’ extensive experience with alcohol, increased speed of metabolism, and lower self-perceived impairment, we show that on a more demanding task they are just as impaired as light drinkers.”

    Brumback is a postdoctoral fellow in addiction treatment with VA and the University of California, San Diego.

    The study results were published in a March 2017 issue of the journal Psychopharmacology.

    Many studies have measured how consuming alcohol impairs both cognitive function and motor coordination. Researchers have also observed that people with histories of heavier prolonged drinking often show greater tolerance to alcohol than lighter drinkers. While research has shown that more experienced drinkers are less impaired by alcohol on some performance measures, the degree to which this tolerance changes over time has not been clearly shown.

    This study sought to answer this question as part of the Chicago Social Drinking Project, led by Dr. Andrea King at the University of Chicago. One-hundred fifty-five young adult volunteers were tested on two cognitive and motor coordination tests at the beginning of the study and again five years later.

    The study defined a heavy drinker as a person who drank between 10 and 40 alcoholic drinks per week for at least the past two years at the initial testing. This involved consuming more than five drinks at one time for men and more than four for women. Light drinkers were those who had fewer than six drinks per week. Participants maintained these drinking habits across the five years between initial testing and follow-up.

    Participants completed two psychomotor tasks. In the Grooved Pegboard Test, they were timed moving, inserting, and rotating pegs into slotted holes on a board. This test measures fine motor skills. In the Digit Symbol Substitution Test (DSST), participants were given a legend with different symbols corresponding to numbers. They then had 90 seconds to fill in the correct symbols on a sheet with numbers. The test is designed to assess not only fine motor skills, but also short-term memory and cognitive processing.

    Brumback explains that a real-world activity such as using keys to unlock a door is similar to manipulating a peg on the Pegboard Test. The DSST is akin to more complex tasks such as remembering directions to a novel location or driving a car.

    Before each test, participants were given a dose of alcohol that was calculated based on their body weight to bring them to a specific breath alcohol concentration. They were then tested at 30, 60, 120, and 180 minutes after the drink.

    As expected, all the participants performed worse on both tests when impaired by alcohol. In a prior report, the authors showed that light and heavy drinkers showed similar levels of impairment on both tasks during the initial testing. At the five-year follow-up, both groups showed improvement on both tasks compared with how they had done when tested years earlier, which the authors attribute primarily to practice effects.

    Heavy drinkers also showed evidence of chemical tolerance to alcohol. Their breath alcohol concentrations decreased faster after drinking at the five-year retest versus the initial test. The result lends support to the idea that heavy drinkers absorb and metabolize alcohol faster than light drinkers.

    While both groups did better at the follow-up, heavy drinkers showed less impairment on the pegboard than light drinkers relative to their initial testing scores. This did not hold true on the DSST, however. Both heavy and light drinkers showed similar levels of impairment during the follow-up testing.

    All in all, the results show that sustained heavier drinking may lead to less impairment in simpler fine motor skills relative to lighter drinking, but this tolerance does not help performance on tasks involving more complex motor processing and short-term memory. Thus, faster metabolization of alcohol in heavy drinkers did not lead to better performance on the more complex task.

    Heavier drinkers may develop behavioral tolerance for several reasons, say the researchers. Repeatedly drinking to intoxication leads to cellular adaptation within the brain, changing the sensitivity to alcohol. Contextual factors also play a part: When people learn a task while drunk, they adapt to performing that task while under the influence.

    A key point the researchers highlight is that heavy drinkers reported lower self-perceived impairment than light drinkers. They suggest that, for heavy drinkers, lower perceived impairment and higher sensitivity to the stimulating and rewarding effects of alcohol could make the habit more dangerous for them. They may engage in more potentially risky behaviors while drunk because they see their impairment level as lower.

    Brumback provides an example of how this could play out in the real world, “Say a heavy drinker is out at a restaurant and becomes intoxicated. When it comes time to leave, this person has only internal and external cues to help make the decision whether to drive home or call a cab. So, if this person tends to perceive herself as less impaired, she gets up from the table and walks to the door, pushes the door open, and walks to her car. These simple motor functions may not provide sufficient feedback for her to decide she is too drunk to drive. Furthermore, when she gets to her car and unlocks the door and even puts the car in gear, she may not be perceiving impairment in these simple tasks. However, once she begins to drive, the cognitive and psychomotor demands increase significantly but the decision to drive has already been made based on the earlier simple tasks.”

    In scenarios such as this, alcohol tolerance may in fact lead heavy drinkers to judge that they are not impaired and attempt more difficult tasks.

    “Overall, there is a common belief among heavy drinkers that they can ‘handle their alcohol’ and that many common daily tasks may not be affected by their alcohol use,” says Brumback. “The take-home message here is that tolerance to alcohol is not equal across all tasks and is not ‘protective’ against accidents or injuries while intoxicated, because it may in fact lead the heavy drinker to judge that they are not impaired and attempt more difficult tasks. Making such decisions in the moment is highly risky, because it is based on faulty information.”


  7. Study suggests oxytocin may help prevent drug addiction relapse

    April 18, 2017 by Ashley

    From the University of St George’s London press release:

    Experts say oxytocin, a key hormone made naturally by the brain, could hold the key to treating drug addicts and help them avoid relapse.

    Oxytocin is most usually associated with childbirth and breast feeding, but has multiple psychological effects, influencing social behaviour and emotion.

    Sometimes called the ‘love hormone’, it has an anti-anxiety effect, and many studies have examined the role of oxytocin in addiction.

    Researchers at St George’s, University of London, after reviewing all the published evidence on oxytocin, have now found that the oxytocin system is profoundly affected by opioid use and abstinence.

    The review, which includes seminal studies conducted by Dr. Alexis Bailey’s group, suggests the oxytocin system can be an important target for developing new medicines for the treatment of opioid addiction and prevention of relapse among addicts.

    Taking drugs activates pathways in the brain that induce pleasurable effects, which make the user want to repeat the experience, but as drug use continues, brain tolerance to the effects of the drug increases and a greater dose is needed to achieve the same effects.

    Dr Alexis Bailey, senior author of the review, said: “Given the benefits that social support programmes like Alcoholics Anonymous and Narcotics Anonymous have in keeping addicts abstinent, our findings in the review suggest the use of oxytocin, the pro-social hormone, could be an effective therapy for the prevention of relapse to drug use in drug-dependent individuals.

    “Since the evidence is so clear, the need for clinical studies looking into this is obvious.”

    The study “Oxytocin and opioid addiction revisited: Old drug, new applications” was published in British Journal of Pharmacology.


  8. Study suggests surprising brain change may drive alcohol dependence

    April 16, 2017 by Ashley

    From the Scripps Research Institute press release:

    A new study led by scientists at The Scripps Research Institute (TSRI) could help researchers develop personalized treatments for alcoholism and alcohol use disorder.

    The research reveals a key difference between the brains of alcohol-dependent versus nondependent rats. When given alcohol, both groups showed increased activity in a region of the brain called the central amygdala (CeA) — but this activity was due to two completely different brain signaling pathways.

    TSRI Professor Marisa Roberto, senior author of the new study, said the findings could help researchers develop more personalized treatments for alcohol dependence, as they evaluate how a person’s brain responds to different therapeutics.

    The findings were published recently online ahead of print in The Journal of Neuroscience.

    Researchers Find Brain’s Alcohol Response ‘Switch’

    The new research builds on the Roberto lab’s previous discovery that alcohol increases neuronal activity in the CeA. The researchers found increased activity both nondependent, or naïve, and alcohol-dependent rats.

    As they investigated this phenomenon in the new study, Roberto and her colleagues were surprised to find that the mechanisms underlying this increased activity differed between the two groups.

    By giving naïve rats a dose of alcohol, the researchers engaged proteins called calcium channels and increased neuronal activity. Neurons fired as the specific calcium channels at play, called L-type voltage-gated calcium channels (LTCCs), boosted the release of a neurotransmitter called GABA. Blocking these LTCCs reduced voluntary alcohol consumption in naïve rats.

    But in alcohol-dependent rats, the researchers found decreased abundance of LTCCs on neuronal cell membranes, disrupting their normal ability to drive a dose of alcohol’s effects on CeA activity. Instead, increased neuronal activity was driven by a stress hormone called corticotropin-releasing factor (CRF) and its type 1 receptor (CRF1). The researchers found that blocking CeA CRF1s reduced voluntary alcohol consumption in the dependent rats.

    Studying these two groups shed light on how alcohol functionally alters the brain, Roberto explained.

    “There is a switch in the molecular mechanisms underlying the CeA’s response to alcohol (from LTCC- to CRF1-driven) as the individual transitions to the alcohol-dependent state,” she said.

    The cellular and molecular experiments were led by TSRI Research Associate and study first author Florence Varodayan. The behavioral tests were conducted by TSRI Research Associate Giordano de Guglielmo in the lab of TSRI Associate Professor Olivier George.

    Roberto hopes the findings lead to better ways to treat alcohol dependence. Alcohol use disorder appears to have many different root causes, but the new findings suggest doctors could analyze certain symptoms or genetic markers to determine which patients are likely to have CRF-CRF1 hyperactivation and benefit from the development of a novel drug that blocks that activity.


  9. Stress flips cocaine relapse to ‘on’; research switches it back to ‘off’

    April 15, 2017 by Ashley

    From the Brown University press release:

    A heartbreaking phenomenon of addiction is that just a brief stressful episode can trigger relapse. In a detailed new cocaine addiction study conducted in rat models, which closely parallel human addictive behavior, scientists have identified what appears to be taking place in the mammalian brain to make that happen and uncovered the molecular biology that allows them to switch the stress-induced relapse back off.

    The findings, published in the journal eLife, suggest a new way to develop medicines to combat relapse, even a day or so after stress has occurred.

    “That’s so critical because you don’t want to be taking medication all the time in anticipation of stress,” said senior author Julie Kauer, a professor of molecular pharmacology, physiology and biotechnology at Brown University.

    How relapse persists

    At the heart of the study are kappa opioid receptors (?ORs) on the surface of key brain cells. The ?ORs are already seen as targets for anti-addiction medication development, but to make effective therapies, researchers must pinpoint specific interactions. In the new study, Kauer’s team of scientists at Brown and the University of Wyoming made observations both in behaving rats and in rat brain tissue to focus on how stress appears to trigger these receptors to cause relapse, how that relapse remains sustained and how that effect can be disrupted.

    The study focused on the ventral tegmental area (VTA), where the brain reinforces behaviors related to fulfilling basic needs. Sometimes those are healthy needs, like food, but they can also be cravings for drugs, alcohol or nicotine. Within the VTA, the reward for fulfilling needs is mediated by neurons that pump out the neurotransmitter dopamine. Those neurons are curbed, however, by the inhibitory neurotransmitter GABA, through connections to other neurons called synapses.

    Neuroscientists have known that, as in people, stress induces relapse in rats. One mechanism is the release of a protein called dynorphin that naturally activates ?ORs. The new study provides evidence that after brief acute stress, dynorphin triggers a long-lasting change in the conformation of the receptors, specifically on the GABA-releasing synapses that inhibit dopamine-releasing neurons in the VTA.

    This specific change, the results suggest, serves to disrupt GABA’s ability to hold back the dopamine neuron activity that may drive cocaine-seeking. Once the conformational change is made in the ?ORs, the researchers found, that relapse-promoting change stays in effect for days without any additional stress or any continued need for dynorphin.

    That ?ORs continue to behave the same way for days even after just one brief stimulus is a new finding in neuroscience, the authors wrote in eLife: “Ours is the first demonstration of experience-induced changes in constitutive activity of these receptors.”

    Reversing relapse

    In a previous paper, the researchers showed that the chemical norBNI could end the relapse. In the new paper, they showed that they could reverse relapse with norBNI in the rats even a full day after stress.

    Now they also know more about how that works. In a key experiment in the new study, they showed that norBNI activates a molecular pathway in the neurons called JNK (pronounced “junk”) to restore the kORs to their normal conformation that does not exhibit sustained signaling. They also showed that merely blocking dynorphin from binding to ?ORs did not restore GABAergic neuron activity and would therefore not be a productive drug development strategy.

    In another experiment, they showed that while relapse can be prevented by blocking dynorphin release before stress occurs, blocking dynorphin release after stress occurs does no good. Dynorphin’s unfortunate work is already done.

    Given their evidence, what Kauer’s team theorizes is that stress, via dynorphin, flips a switch on ?ORs that turns off normal GABA signaling at the relevant synapses for days. Using norBNI is like flipping another switch, via JNK, that rescues normal GABA signaling.

    In human pharmacology, Kauer acknowledged, norBNI is not favored because its effects persist for weeks and could cause unwanted side effects, but that’s why it’s helpful to know that it exploits the JNK pathway to do its work.

    “JNK is going to be an important future avenue to go down,” Kauer said. “Maybe you could use something other than norBNI to drive JNK.”

    That, in turn, could someday provide people who have recovered from cocaine addiction with a medicine that prevents to the return of cravings because of stress.


  10. Broad support exists for larger warnings on cigarette packs

    April 1, 2017 by Ashley

    From the UNC Lineberger Comprehensive Cancer Center press release:

    Health warnings cover about 10 percent of a cigarette pack’s exterior surface in the United States, but there is broad support, even among smokers, for making them significantly larger, a University of North Carolina Lineberger Comprehensive Cancer Center study has found.

    The study, published in the journal PLoS ONE, found that a majority of smokers and nonsmokers who responded to a randomized telephone survey said they supported increasing warning sizes to cover 25 percent, 50 percent, and as much as 75 percent of cigarette packs. The data was presented in a poster session at the National Conference on Tobacco or Health.

    “These findings show there is national public support for implementing larger pack warnings in the United States,” said Adam Goldstein, MD, MPH, a UNC Lineberger member and professor in the UNC School of Medicine Department of Family Medicine. “There’s broad support, even among smokers.”

    Previous research has suggested that larger sized warnings on cigarette packs are more effective than smaller warning labels in increasing smokers’ intentions to quit and leading them to think about the harms of smoking, said the study’s first author Sarah Kowitt, a doctoral student in the UNC Gillings School of Global Public Health.

    While a federal law passed in 2009 called for larger cigarette warnings, litigation has stalled the enactment of the warning requirements. The 2009 Family Smoking Prevention and Tobacco Control Act required the U.S. Food and Drug Administration to implement graphic, or picture, warnings along with text covering half of the front and rear panels of cigarette packages. These warnings have not yet been implemented because of tobacco industry lawsuits, and the U.S. FDA is researching new warnings to comply with any legal challenges.

    In a telephone survey of 5,014 U.S. adults, researchers gauged whether respondents would support larger warning sizes. Respondents were asked about their opinions about a warning covering either 25, 50, or 75 percent of the cigarette pack. They found that more than 78 percent of all respondents and 75 percent of smokers, supported a warning covering 25 percent of a pack. Seventy percent of respondents supported a warning covering half of the pack, and 58 percent of smokers did. For a warning covering 75 percent of a pack, nearly 68 percent of respondents and 61 percent of smoker supported an increase.

    They also found that smokers intending to quit smoking responded to the questions about increasing pack size by 25 and 50 percent more favorably.

    “Most adults, including smokers, have favorable attitudes towards larger warning labels on cigarette packs,” Kowitt said. “These findings support the implementation of larger health warnings on cigarette packs in the U.S. as required by the 2009 Tobacco Control Act.”