1. Higher estrogen levels linked to increased alcohol sensitivity in brain’s ‘reward center’

    November 14, 2017 by Ashley

    From the University of Illinois at Chicago press release:

    The reward center of the brain is much more attuned to the pleasurable effects of alcohol when estrogen levels are elevated, an effect that may underlie the development of addiction in women, according to a study on mice at the University of Illinois at Chicago.

    Led by Amy Lasek, assistant professor of psychiatry in the UIC College of Medicine, researchers found that neurons in a region of the brain called the ventral tegmental area, or VTA (also known as the “reward center”), fired most rapidly in response to alcohol when their estrogen levels were high. This response, according to their findings published online in the journal PLOS ONE, is mediated through receptors on dopamine-emitting neurons in the VTA.

    “When estrogen levels are higher, alcohol is much more rewarding,” said Lasek, who is the corresponding author on the paper and a researcher in the UIC Center for Alcohol Research in Epigenetics. “Women may be more vulnerable to the effects of alcohol or more likely to overindulge during certain stages of their cycle when estrogen levels are higher, or may be more likely to seek out alcohol during those stages.”

    Studies indicate that gender differences in psychiatric disorders, including addiction, are influenced by estrogen, one of the primary female sex hormones. Women are more likely to exhibit greater escalation of abuse of alcohol and other drugs, and are more prone to relapse in response to stress and anxiety.

    The VTA helps evaluate whether something is valuable or good. When neurons in this area of the brain are stimulated, they release dopamine — a powerful neurotransmitter responsible for feelings of wellness — and, in large doses, euphoria. When something good is encountered — for example, chocolate — the neurons in the VTA fire more rapidly, enforcing reward circuitry that encodes the idea that chocolate is enjoyable and something to be sought out. Over time, the VTA neurons fire more quickly at the sight, or even thought of, chocolate, explained Lasek. In addiction, VTA neurons are tuned into drugs of abuse, and fire more quickly in relation to consuming or even thinking about drugs, driving the person to seek them out — often at the expense of their own health, family, friends and jobs.

    Many animal studies have shown that alcohol increases the firing of dopamine-sensitive neurons in the VTA, but little is known about exactly why this occurs.

    Lasek and her colleagues examined the relationship between estrogen, alcohol and the VTA in female mice. They used naturally cycling mice that were allowed to go through their normal estrous cycles, akin to the menstrual cycle in women.

    Mice were evaluated to determine when they entered diestrus — the phase in the estrous cycle when estrogen levels are close to their peak.

    “In mice in diestrus, estrogen levels increase to about 10 times higher than they are in estrus, the phase in which ovulation occurs and estrogen levels drop,” Lasek said.

    VTAs were taken from mice in both estrus and diestrus and kept alive in special chambers. Electrodes recorded the activity of individual dopamine-sensitive neurons in the VTA. Next, the researchers added alcohol to the chamber. Activity increased twice as much in neurons from mice in diestrus compared to the response of neurons from mice in estrus.

    Lasek and her colleagues then blocked estrogen receptors on dopamine-sensitive neurons in VTA in mice in estrus and diestrus. With the blocker present, the response to alcohol in neurons from mice in diestrus was significantly lower compared with neurons where estrogen receptors remained functional. The estrogen receptor blocker reduced the alcohol response to levels seen in mice in estrus. The responses to alcohol in neurons from mice in estrus were unaffected by the estrogen receptor blocker.

    “The increased reward response to alcohol we see when estrogen levels are high is mediated through receptors for estrogen in the VTA,” said Mark Brodie, professor of physiology and biophysics in the UIC College of Medicine and a co-author on the paper.

    Lasek believes that the increased sensitivity to alcohol in the VTA when estrogen levels peak may play a significant role in the development of addiction in women.

    “We already know that binge drinking can lead to lasting changes in the brain, and in women, those changes may be faster and more significant due to the interaction we see between alcohol, the VTA and estrogen,” Lasek said. “Binge drinking can increase the risk of developing alcoholism, so women need to be careful about how much alcohol they drink. They should be aware that they may sometimes inadvertently over-consume alcohol because the area of the brain involved in alcohol reward is responding very strongly.”


  2. Study suggests frequent alcohol drinking kills new brain cells in adults, females are more vulnerable

    November 13, 2017 by Ashley

    From the University of Texas Medical Branch at Galveston  press release:

    Researchers from The University of Texas Medical Branch at Galveston recently discovered that alcohol killed the stem cells residing in adult mouse brains. Because the brain stems cells create new nerve cells and are important to maintaining normal cognitive function, this study possibly opens a door to combating chronic alcoholism.

    The researchers also found that brain stem cells in key brain regions of adult mice respond differently to alcohol exposure, and they show for the first time that these changes are different for females and males. The findings are available in Stem Cell Reports.

    Chronic alcohol abuse can cause severe brain damage and neurodegeneration. Scientists once believed that the number of nerve cells in the adult brain was fixed early in life and the best way to treat alcohol-induced brain damage was to protect the remaining nerve cells.

    “The discovery that the adult brain produces stem cells that create new nerve cells provides a new way of approaching the problem of alcohol-related changes in the brain,” said Dr. Ping Wu, UTMB professor in the department of neuroscience and cell biology. “However, before the new approaches can be developed, we need to understand how alcohol impacts the brain stem cells at different stages in their growth, in different brain regions and in the brains of both males and females.”

    In the study, Wu and her colleagues used a cutting-edge technique that allows them to tag brain stem cells and observe how they migrate and develop into specialized nerve cells over time to study the impact of long-term alcohol consumption on them.

    Wu said that chronic alcohol drinking killed most brain stem cells and reduced the production and development of new nerve cells.

    The researchers found that the effects of repeated alcohol consumption differed across brain regions. The brain region most susceptible to the effects of alcohol was one of two brain regions where new brain cells are created in adults.

    They also noted that female mice showed more severe deficits than males. The females displayed more severe intoxication behaviors and more greatly reduced the pool of stem cells in the subventricular zone.

    Using this model, scientists expect to learn more about how alcohol interacts with brain stem cells, which will ultimately lead to a clearer understanding of how best to treat and cure alcoholism.

    Other authors include UTMB’s Erica McGrath, Junling Gao, Yong Fang Kuo, Tiffany Dunn, Moniqua Ray, Kelly Dineley, Kathryn Cunningham and Bhupendra Kaphalia.


  3. Study suggests smoking, binge drinking and unsafe tanning may be linked in men

    November 11, 2017 by Ashley

    From the University of Connecticut press release:

    Even though men use tanning beds at lower rates than women, men who tan tend to do it in riskier ways, according to a study by researchers at the University of Connecticut. The findings should help public health officials rethink how, and to whom, they’re targeting anti-tanning messages.

    Because the stereotypical tanning salon client is a young woman, almost all the research and health messaging on tanning has focused on that demographic. But the new research in press in the Journal of the American Academy of Dermatology found that one in three people who use tanning beds in the U.S. are male.

    Men who tan report using tanning beds with about the same frequency as women, but smoke and binge drink at higher rates than their female counterparts, and they also tend to treat tanning more like an addiction than women do, say the authors. A full 49 percent of men who used tanning beds fit a pattern of addictive behavior around tanning.

    “That was really surprising,” says lead author Sherry Pagoto, a clinical psychologist and director of the UConn Center for mHealth and Social Media. “If they tan with the same frequency as women, why would tanning in men be more addictive?”

    Pagoto and her colleagues conducted a national survey of 636 people who answered “yes” when asked whether they had ever used a tanning bed. They queried the participants about frequency of use, preferred locations to tan, how they felt about tanning, and why they did it.

    The differences between men and women were marked. Women preferred to tan in salons, and said they valued low cost, cleanliness, and convenience. Men who tanned preferred less regulated settings, such as gyms or private homes. They said they liked to tan to accentuate the appearance of their muscles, or as a reward after working out. They also reported smoking tobacco, binge drinking alcohol, and drinking soda significantly more often than women who tan.

    Men also answered “yes” when asked if they ever felt anxious if they weren’t able to tan, tanned to relieve stress, or spent money on tanning even when they couldn’t afford it. They agreed with statements such as “I’d like to quit but I keep going back to it.”

    There’s a population of men who tan and engage in other risky behaviors and are very unlike the young women that health educators assume are at risk of tanning bed health impacts, says Pagoto.

    Pagoto and her team are pursuing another study to delve more deeply into who tans, asking questions about sexual orientation, given that recent research has revealed that homosexual men are just as likely to use tanning beds as young women. The research should help health officials trying to warn the public of the very real connection between tanning beds and skin cancer, she says.

    Sun lamps and tanning beds are legal for adult use in all 50 states, even though the Food and Drug Administration (FDA) classifies them as a Class 1 carcinogen like tobacco, radon, and arsenic, and the use of tanning beds has been linked to melanoma, the deadliest form of skin cancer.

    Most current marketing messaging is targeted to teen- and college-aged women, according to Pagoto. Men who tan are unlikely to relate to that type of message. Pagoto is now applying social media marketing principles to develop prevention messages that resonate with specific audience segments.

    “We’re also hoping to spread the message on college campuses, since the tanning industry heavily markets to college students,” she says.


  4. Study looks at how gut and gender may affect ease of quitting smoking

    November 6, 2017 by Ashley

    From the American Chemical Society:

    Many people who smoke or chew tobacco can’t seem to escape nicotine’s addictive properties. Studies show that women in particular seem to have a harder time quitting, even with assistance, when compared to men. Now, scientists report in a mouse study published in ACS’ journal Chemical Research in Toxicology that the difference in gender smoking patterns and smoking’s effects could be due to how nicotine impacts the brain-gut relationship.

    Cigarette smoking has long been a major public health issue. It’s related to one out of every five deaths in the U.S., according to the U.S. Centers for Disease Control and Prevention. When a person smokes tobacco, nicotine is delivered mainly to the lungs. But with skin patches and chewing tobacco, nicotine crosses the skin and into the gastrointestinal tract, respectively. Previous research has shown that nicotine and the nervous system interact, producing a number of effects including the release of the “feel-good” chemical dopamine. Studies have also shown that the effects of nicotine are gender-dependent. To more fully understand why this is, Kun Lu and colleagues wanted to explore how nicotine affects male and female gut microbiomes.

    The researchers set up a 13-week experiment during which they administered nicotine-infused water to mice. An analysis of the animals’ fecal samples showed major differences in the composition of the microbiomes in male and female mice. Levels of compounds and bacterial genes associated with the nervous system and body weight were altered in different ways in male and female mice. For example, the mice exposed to nicotine, especially the males, had lower concentrations of glycine, serine, and aspartic acid, which could weaken the addictive effect of nicotine. In addition, nicotine-treated female mice had reduced amounts of Christensenellaceae bacteria, while the treated male mice had increased levels, which are associated with a lower body mass index. The team says future efforts will focus on exploring the relationship of the nicotine-gut-brain interactions on a molecular level to further understand the communication paths involved.


  5. Study suggests effectiveness of online social networks designed to help smokers quit

    November 1, 2017 by Ashley

    From the University of Iowa press release:

    Online social networks designed to help smokers kick the tobacco habit are effective, especially if users are active participants, according to a new study from the University of Iowa and the Truth Initiative, a nonprofit anti-tobacco organization.

    The study examined the tobacco use of more than 2,600 smokers who participated in BecomeAnEX.org, Truth Initiative’s online smoking cessation community designed in collaboration with the Mayo Clinic. The study found that 21 percent of those classified as active users after their first week in the community reported that they quit smoking three months later. Those who were less active in the community were less likely to quit.

    Kang Zhao, assistant professor of management sciences in the UI Tippie College of Business and the study’s co-author, says the results show that online interactions can predict offline behavior.

    How central you become in the online social network after the first week is a good indicator of whether you will quit smoking,” says Zhao. “This is the first study to look at smokers’ behaviors in an online community over time and to report a prospective relationship between social network involvement and quitting smoking.”

    The BecomeAnEX website enables members to share information and support through blogs, forums, and messages. Although the site is focused on smoking cessation, users can post on any topic. More than 800,000 users have registered since the site launched in 2008, resulting in a large, active community of current and former tobacco users supporting each other.

    Funded by the National Cancer Institute, the study constructed a large-scale social network based on users’ posting habits. Zhao says a key finding was that increasing integration into the social network was a significant predictor of subsequent abstinence. Three months after joining the BecomeAnEX social network, users who stayed involved on the site were more likely to have quit smoking when researchers contacted them to assess their smoking status.

    After three months, 21 percent of active users — or those who actively contributed content in the community — quit smoking; 11 percent of passive users — those who only read others’ posts — quit smoking; and only 8 percent of study participants that never visited quit smoking.

    The study did not examine why greater community involvement had such a positive effect on smoking cessation. Researchers speculate it may be because of powerful social network influences.

    “Spending time with others who are actively engaged in quitting smoking in a place where being a nonsmoker is supported and encouraged gives smokers the practical advice and support they need to stay with a difficult behavior change,” says Amanda Graham, senior vice president, Innovations, of Truth Initiative and lead author. “We know that quitting tobacco can be extremely difficult. These results demonstrate what we hear from tobacco users, which is that online social connections and relationships can make a real difference.”


  6. Study links dependence on indoor tanning devices with beliefs about physical appearance and depressive symptoms

    October 21, 2017 by Ashley

    From the American Association for Cancer Research press release:

    More than 20 percent of non-Hispanic white women ages 18 to 30 who reported using an indoor tanning device one or more times in the past 12 months were dependent on indoor tanning. Dependence was strongly associated with beliefs about physical appearance and depressive symptoms, outlined in a new report published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research. The lead author is Darren Mays, PhD, MPH, assistant professor at Georgetown University Medical Center in Washington, D.C., and member of the Cancer Prevention and Control Program at the Georgetown Lombardi Comprehensive Cancer Center.

    Indoor tanning increases a person’s risk for melanoma, the most deadly form of skin cancer, by about 20 percent, according to The Surgeon General’s Call To Action To Prevent Skin Cancer. It also increases risk for other forms of skin cancer.

    Mays explained that although indoor tanning is becoming less common overall in the United States, research indicates that it can be a problematic behavior for some young women similar to other forms of addiction. If we are to reduce this risky behavior and ultimately reduce skin cancer risks, we must understand what factors — such as behaviors, beliefs, and psychological comorbidities — are associated with indoor tanning dependence, he added.

    The researchers studied indoor tanning dependence and the factors associated with it in young adult non-Hispanic white women because this group has the highest prevalence of indoor tanning in the U.S. adult population, according to Mays.

    Three-hundred and eighty-nine non-Hispanic white women ages 18 to 30 who had used an indoor tanning device one or more times in the prior 12 months completed online questionnaires; 46.7 percent of the participants were current college or university students. Indoor tanning dependence was assessed using two questionnaires modified from screeners for other addictive behaviors, the CAGE and Diagnostic and Statistical Manual for Mental Disorders (DSM) screeners. To be classed as dependent on indoor tanning, individuals had to screen positive on both modified questionnaires.

    Overall, 22.6 percent of participants screened positive for indoor tanning dependence. In bivariate analysis, those who screened positive were more likely to have started tanning at an earlier age, be concerned about their appearance, and have depressive symptoms.

    Further analysis showed that indoor tanning dependence was strongly associated with beliefs about physical appearance and depressive symptoms. As women’s beliefs that appearance is important grew stronger, they were 73 percent more likely to screen positive for indoor tanning dependence. Women who screened positive for depressive symptoms were almost four times as likely to screen positive for indoor tanning dependence than those who did not have depressive symptoms.

    “Our study has identified a subgroup of young adult women who are dependent on indoor tanning,” saidd Mays. “These young women are unlikely to respond to public health messaging and we will need to develop a more intensive resource to motivate behavior change. Given that we found strong associations between indoor tanning dependence and beliefs about physical appearance and psychological comorbidities like depression, these intensive behavior-modification resources likely need to address these co-occurring psychological concerns.

    “One of the next steps is to develop and test interventions to address indoor tanning dependence,” he continued. “There is very little research in this area, so we may need to draw from successful approaches to changing behaviors like cigarette smoking.”

    According to Mays, the main limitation of the study is that the researchers analyzed indoor tanning dependence in a group of young women from a single geographic area, the Washington, D.C. metropolitan area. Thus, the findings may not be the same for the entire population or other groups, such as young men.


  7. Study suggests that learning about slot-machine tricks can help new players avoid gambling addiction

    October 20, 2017 by Ashley

    From the University of Waterloo press release:

    Novice gamblers who watched a short video about how slot machines disguise losses as wins have a better chance of avoiding gambling problems, according to new research.

    Slot machines present losses disguised as wins (LDWs) with celebratory music and flashing lights, even though players actually won less money than they bet. People can mistakenly believe that they are winning and continue paying to play.

    Researchers at the University of Waterloo found that showing inexperienced gamblers a brief educational video before they play helps make them more aware and curb false perceptions about the number of times they won.

    “One of the keys to gambling harm prevention is to curtail misperceptions before they become ingrained in the minds of gamblers,” said Michael Dixon, professor and research director in the Gambling Research Lab at Waterloo. “By exposing these outcomes for what they are, our study shows a way in which we can lead slots gamblers to have a more realistic view of their gambling experiences and possibly prevent problems down the road.”

    Earlier research from the University’s Gambling Research Lab found that LDWs can also lead players to gamble for longer even when they are losing money — a symptom of gambling addiction.

    As part of this study, one group of participants watched an educational video on slot machines and how they present LDWs, while a second group watched a different, unrelated video. All participants then played two games, one with few LDWs and one with many LDWs. They then had to estimate the number of times they won more than they wagered on each game.

    “We found that the video was effective in correcting multiple misperceptions. Players not only remembered their actual number of wins more correctly, but they were also more capable of labelling losses disguised as wins during slot machine play,” said Candice Graydon, lead author and a PhD candidate in Waterloo’s Department of Psychology at the time of this study. “We’d like to assess whether shining the light on LDWs will make gamblers stop playing sooner.”

    On the many LDW games, both groups got actual wins on approximately 10 per cent of spins. The group that did not watch the video drastically overestimated their wins — believing won on 23 per cent of spins. The group that watched the educational video, however, gave accurate win estimates. They recalled winning on only 12 per cent of spins. The study suggests that novice players who view the educational video will become more aware of LDWs, which could make them more attentive to other slot features such as the running total counter. Researchers would like to see the animation available to players both online and on casino floors.


  8. Study suggests cocaine use during adolescence is even more harmful than during adulthood

    October 19, 2017 by Ashley

    From the Fundação de Amparo à Pesquisa do Estado de São Paulo press release:

    People who begin using cocaine during adolescence display more significant cognitive deficits than people who begin using the drug in adulthood. That which experts in neuroscience have long suspected has been given an objective confirmation by researchers working at the University of São Paulo’s Medical School (FM-USP), in Brazil.

    When scientists compared the two groups of cocaine users, they observed pronounced differences, mainly in specific neuropsychological functions such as sustained attention (required for performing long tasks, such as completing a questionnaire), working memory (used in specific actions, for example, a waiter remembering the order of each table until the time comes to deliver the orders) and declarative memory (storing and retrieving data after a period of time).

    They also found that among early-onset users, the concurrent consumption of cannabis and alcohol was 50% and 30% more frequent, respectively, compared with late-onset users, defined as those who began using cocaine at or over the age of 18. The complete findings of the research project, which was supported by the São Paulo Research Foundation — FAPESP, were published in the journal Addictive Behaviors.

    Adolescence is considered one of the key stages of brain development when surplus synapses are eliminated and the structures essential to adulthood are selected and refined. Drug use in this stage can impair the brain programming process and lead to the loss of important connections,” said Paulo Jannuzzi Cunha, a professor at FM-USP and principal investigator for the project.

    Differentiated Methodology

    According to Cunha, one of the novel aspects of the research project conducted at the Psychiatry Institute of Hospital das Clínicas, FM-USP’s teaching and general hospital, was the measurement of cognitive functions during controlled abstinence.

    “Many studies of this kind assess outpatients without any possibility of knowing whether they’ll use drugs when they go home,” he said. “In our case, however, all participants were hospital inpatients. We can, therefore, be sure the findings didn’t reflect acute effects of cocaine or other substances.”

    The sample contained 103 cocaine-dependent patients, 52 of whom were early-onset users who had begun using the drug before they were 18, while 51 were late-onset users who began when they were 18 or older. All individuals were evaluated after at least a week of abstinence. The absence of cocaine metabolites was verified by toxicological urine tests. A third group of 63 people with no history of psychoactive substance use served as the control.

    The participants’ ages ranged from 20 to 35. The proportions of men and women were similar. One of the early-onset users had begun consuming cocaine at age 12.

    “Data in the scientific literature shows that a brain region called the prefrontal cortex continues to develop until age 25. This region relates to what are known as executive functions, such as planning, decision making, inhibitory control, attention, and working memory. We, therefore, decided to investigate whether these functions were more impaired in early-onset users,” said psychologist Bruna Mayara Lopes, first author of the article.

    The evaluation involved a number of tests, including the Frontal Assessment Battery (FAB), Stroop Color Word Test (SCWT), Controlled Oral Word Association Test (COWAT), Wisconsin Card Sorting Test (WCST), Rey Osterrieth Complex Figure Test (ROCFT) and Iowa Gambling Task (IGT). The use of alcohol and other drugs was assessed using the Addiction Severity Index (ASI-6).

    “Basically, we presented the participants with a task they had to complete, such as repeating a sequence of numbers in reverse order or reproducing a figure from memory about 30 minutes after observing it,” Lopes said.

    When they compared late-onset users with the control group and adjusting the results for variables such as age and intelligence quotient (IQ), the only difference the researchers found was in divided attention, which relates to the ability to perform multiple tasks at the same time.

    Going deeper

    In a study under way at USP’s Neuroimaging Laboratory (LIM-21), the researchers are now seeking to correlate the cognitive profile observed in the two groups of cocaine-dependent patients with decision-making and resting-state brain activity, using functional magnetic resonance imaging (fMRI). Studies of brain structure and correlations with levels of a protein known as BDNF (brain-derived neurotrophic factor) will also be performed using these findings.

    “We’re measuring such variables as prefrontal cortex volume and white matter integrity. We’ll be able to disclose some of our findings shortly,” said Priscila Dib Gonçalves, supervisor of the Psychology & Neuropsychology Service at the Psychiatry Institute and co-author of the article.

    White matter, found in the deeper tissues of the brain, contains axons connecting grey matter, which is where all synapses are located.

    According to Gonçalves, a higher probability of cognitive impairment due to early-onset drug use was already observed in a study involving 104 chronic cannabis users. This study, published in 2011 in the British Journal of Psychiatry, was conducted at the Federal University of São Paulo (UNIFESP) by Maria Alice Fontes. It found that people who began smoking marijuana before age 15 underperformed late-onset users in tests that assessed executive functions.

    For Gonçalves, both studies evidence the need to develop more effective prevention strategies and programs targeting adolescents. “We live in a society that associates recreation with the use of psychoactive substances, and this is an important cultural aspect,” she said. “One way to raise awareness of the risks could be to hold workshops with students, who should be called on to play a leading role in this awareness-raising process, rather than being passive recipients of information.”

    For Cunha, the results also show that patients with severe cognitive deficits need intense multidisciplinary treatment, including medication as well as therapy.


  9. Epigenetic study untangles addiction and relapse in the brain

    October 6, 2017 by Ashley

    From the Medical University of South Carolina press release:

    Why do some drug users continue to seek out drugs despite the prospect of losing family, friends, health or livelihood?

    There are notable features — cues — of the early drug-using environment that often develop into persistent and powerful triggers for relapse. Epigenetic factors — enzymes in the brain that alter the packaging and accessibility of genes without changing the genes themselves — influence this process, according to research at the Medical University of South Carolina (MUSC) appearing online on September 27, 2017 in Neuron.

    A major challenge in addiction science is to understand how transient experiences lead to long-lasting risk for relapse in users who try to quit, according to MUSC professor Christopher W. Cowan, Ph.D., William E. Murray SmartState® Endowed Chair in Neuroscience, and senior researcher on the project. “Our goal was to discover the brain mechanisms responsible for the rewarding effects of the drug and the motivation to seek it even after long periods of abstinence,” says Cowan.

    The brains of drug users who have progressed to addiction differ markedly from those of early or casual users. Long-lasting associations form between the early use of a drug and different aspects of the early drug-using environment, such as the location in which a drug was first taken or the emotions a user was experiencing at the time. This can cause addicted users who have quit to experience cravings when in a similar setting. Understanding these connections could lead to better treatments for addiction.

    Cowan’s challenge was to determine which genes were activated in the early drug-using environment. Cowan and his fellow researchers had previously found that the epigenetic enzyme histone deacetylase 5 (HDAC5) slows the rodent brain from forming associations between cocaine and simple cues in the environment, such as light and sound. HDAC5 is found in high amounts in neurons in the nucleus accumbens, part of the reward center of the brain that reacts strongly to cocaine, opioids and alcohol — both in rodents and humans. When HDACs are in the nucleus of neurons, they change the way genomic DNA is packaged in the cell nucleus and often block the ability of certain genes to be turned on.

    In the new study, rodents were trained to press a lever to receive a dose of cocaine. Each time they received a dose, a lamp went on above the lever and a brief sound was generated. These served as simple environmental cues for drug use. Next, some rodents were given a form of HDAC5 that traveled straight to the nuclei of neurons. Those rodents still pressed the lever just as many times to receive drug, meaning that HDAC5, on its own, was likely not blocking genes that promoted early drug-seeking behavior.

    Yet the next experiment proved that HDAC5 reduced drug-seeking behavior during abstinence. To simulate withdrawal and abstinence, rodents were given rest without cocaine for one week, followed by a period during which they had access to the lever again. To simulate relapse, the rodents were shown the environmental cues again, this time without having pressed the lever. The presentation of the cues triggered robust lever pressing, indicating drug seeking, in control animals, proving that the associations between drug and environment persisted in their brains. In contrast, animals who had the nuclear form of HDAC5 did not press the lever nearly as often, even after the experimenters gave the animals a small priming dose of cocaine, which often produces strong drug-seeking behaviors.

    HDAC5, the gene suppressor, did not prevent addiction-like behaviors from forming, but it did prevent later drug seeking and relapse during abstinence — at least in rodents.

    The researchers next used a cutting-edge technique that encourages epigenetic enzymes to bind to DNA, allowing them to identify all the genes inhibited by HDAC5. The gene for NPAS4 was a top hit, and significant for an important reason: it is an early-onset gene, meaning that its effects could be exerted on the brain rapidly unless HDAC5 was there to inhibit it — just the molecular event Cowan and his team were seeking.

    In similar experiments, animals with less NPAS4 in the nucleus accumbens took more time to form those early connections between environmental cues and cocaine, but they still sought the drug just as often during later simulated relapse. Apparently, NPAS4 accounts for some addiction-related learning and memory processes in the brain, but not all of them, meaning that HDAC5 must be regulating additional genes that reduce relapse events. Cowan thinks uncovering additional downstream genes could help researchers untangle the details of how the brain transitions from early drug use to addiction, and how new treatments might be developed to reduce relapse in individuals suffering from substance use disorders.

    Animals in the research setting may not mimic the full complexity of human addiction. However, abstinent patients report cravings when given reminders of their drug-associated environment or cues, and animals and humans share similar enzyme pathways and brain structures. Perhaps most exciting for addiction research is that these processes may be similar in the transition to cocaine, alcohol and opioid addictions. “We might have tapped into a mechanism with relevance to multiple substance use disorders,” says Cowan.


  10. Study suggests binge drinking in college may lower chances of landing a job after college

    October 1, 2017 by Ashley

    From the American Friends of Tel Aviv University press release:

    Heavy drinking six times a month reduces the probability that a new college graduate will land a job by 10 percent, according to Tel Aviv University and Cornell University research published in the Journal of Applied Psychology.

    Previous studies were unable to determine the precise effect of alcohol consumption on first-time employment. But according to the new study, each individual episode of student binge-drinking during a month-long period lowers the odds of attaining full-time employment upon graduation by 1.4 percent.

    “The manner in which students drink appears to be more influential than how much they drink when it comes to predicting the likelihood of getting a job upon graduation,” says Prof. Peter Bamberger of TAU’s Coller School of Business Management and Cornell University, who co-authored the study with Prof. Samuel Bacharach of Cornell University; Prof. Mary Larimer and Prof. Irene Geisner, both of the University of Washington; Jacklyn Koopmann of Auburn University; Prof. Inbal Nahum-Shani of the University of Michigan; and Prof. Mo Wang of the University of Florida.

    “Binge-drinking” is defined as ingesting four or more alcoholic drinks within two hours by a woman and five or more alcoholic drinks within two hours by a man, according to the National Institute on Alcohol Abuse and Alcoholism.

    How often, not how much

    The research found that a non-binge pattern of drinking does not adversely impact job search results unless and until their drinking reaches binge levels.

    Data for the study was provided by 827 individuals who graduated in 2014, 2015, and 2016 from Cornell, the University of Washington, the University of Florida, and the University of Michigan.

    “A student who binge-drinks four times a month has a 6 percent lower probability of finding a job than a student who does not engage in similar drinking habits. Those students who drank heavily six times a month increased their unemployment probability to 10 percent,” says Prof. Bamberger.

    Funded by a $2.2 million grant from the National Institute on Alcoholism and Alcohol Abuse, the research is the first installment of a longitudinal study on how alcohol misuse affects the college-to-work transition. More than 16,000 individuals have been contacted as part of the five-year study.

    “This paper is consistent with the recent emphasis on the impact of drinking behavior on career transition from Cornell’s Smithers Institute,” said Prof. Bacharach. “It is in concert with the previous work we’ve done on retirement, and on-boarding [the entry and socialization of newcomers into an organization]. Most importantly, it is also consistent with the Smithers Institute’s continued programmatic interest in substance abuse not only in the workplace, but in the college community as well.”