Brain activity patterns may provide clues about a young person’s risk for initiating harmful alcohol use, according to new research supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA).
NIAAA-funded scientists led by Susan Tapert, Ph.D., and Lindsay Squeglia, Ph.D., of the University of California, San Diego, School of Medicine, and VA San Diego Healthcare, used magnetic resonance imaging (MRI) scans to measure brain activity patterns among 12- to 16-year-old non-drinkers who performed a memory task while being scanned. The researchers repeated the MRI scans three years later, after some of the study subjects had begun to drink heavily.
As reported online in the Journal of Studies on Alcohol and Drugs on August 8, the researchers found that the initial MRI scans of teens who became heavy drinkers had shown less activity in brain regions involved in performing the memory task. They suggest that the decreased brain activity indicates a possible pre-existing vulnerability to harmful drinking—a signal that youth with less activity were more likely to become heavy drinkers.
Three years later, the heavy-drinking teens showed more activity in the same brain regions compared to teens who remained nondrinkers, an indication that the brains of the heavy drinking teens were processing information less efficiently than the nondrinkers’ brains. Researchers explained that, as brains get older, and more efficient, they normally require less effort to accomplish a task, the opposite of what was seen in the heavy drinkers.
“These preliminary findings suggest that we may be able to find neural markers that signal a teen’s risk for heavy drinking even before they start drinking,” notes Ellen Witt, Ph.D., deputy director of the NIAAA division of neuroscience and behavior. “This study points to the need for larger, long-term studies to differentiate the effects of pre-existing neural factors from alcohol’s specific effects on cognition and brain function during adolescence.”
New research by NIAAA scientists shows that an experimental drug that targets molecular sites in the liver and other tissues without acting on identical sites in the brain, holds promise as an effective treatment for obesity and its complications.
In the July 26, 2012 issue of the journal Cell Metabolism, researchers led by NIAAA Scientific Director George Kunos, M.D., Ph.D., and lead author Joseph Tam, D.M.D., Ph.D., of the NIAAA Laboratory of Physiologic Studies, reported that obese mice that were given the new drug, called JD5037, for about a month lost more than one-fourth of their body weight, and had a reduced appetite for the high-fat diet that had made them obese.
"This is a very promising finding,” says NIAAA acting director Kenneth R. Warren, Ph.D. “Obesity is one of our most pressing public health problems, for which new therapies are urgently needed.”
The current findings are part of ongoing studies by Dr. Kunos and his colleagues on the endocannabinoid system, which regulates appetite and the metabolism of lipids, and is therefore implicated in obesity, diabetes, alcoholism and cardiovascular disease.
While drugs that block brain receptors for endocannabinoids have been found to effectively treat obesity, they also cause serious psychiatric side effects, including anxiety and depression. To try to overcome those side effects, Dr. Kunos and his colleagues tested JD5037, which blocks endocannabinoid receptors in the liver, fatty tissue, kidney, skeletal muscle, and other parts of the body – but not those in the brain.
In addition to weight loss, obese mice that were given JD5037 experienced improved metabolic health, such as reduced insulin resistance, compared with obese mice not given the drug. And as hoped, the drug produced no changes in mouse behavior that would predict psychiatric side effects in people.
Dr. Kunos says the new drug appears to make obese mice more sensitive to leptin, an endogenous hormone that suppresses appetite. He explained that, in obesity, the body becomes less responsive to leptin’s appetite-suppressing effect.
"By sensitizing the body to naturally occurring leptin, the new drug could not only promote weight loss, but also help maintain it," he said.
Next research steps for JD5037 include studies to determine whether it’s safe for humans. Such studies are underway, said Dr. Kunos.
Research shows that primary health care providers can promote significant, lasting reductions in drinking levels and alcohol-related problems by asking patients about alcohol use and briefly advising them to reduce risky drinking. In a new study, researchers supported by NIAAA showed that doctors and nurses in an emergency department can also do effective brief interventions for patients who report risky alcohol use. Researchers asked patients who came to the emergency department of a large university hospital about their alcohol use. The nearly 900 adult patients included in the study were found to exceed NIAAA guidelines for low-risk drinking: no more than four drinks in a day and no more than 14 drinks per week for men, and three or fewer drinks per day and no more than seven drinks per week for women. Individuals who received a seven-minute counseling session from a trained emergency practitioner subsequently had significantly lower rates of alcohol consumption and driving after drinking than those who did not, an effect that persisted even a year after the counseling session.
Neuropeptide Y (NPY) is a naturally-occurring brain molecule that helps regulate emotional behavior, stress responses, and other functions. Much research evidence suggests that NPY also plays an important role in regulating alcohol consumption. Scientists led by NIAAA Clinical Director Markus Heilig, M.D., Ph.D., recently investigated the effect of NPY on stress-induced relapse to alcohol use. Relapse prevention is an important aspect of alcoholism treatment, and researchers who study this phenomenon often rely on animal models of relapse-like behavior. Such models usually involve training laboratory rats to obtain alcohol by pressing a lever. Later, the lever-pressing behavior is "extinguished," or unlearned, by removing the alcohol reward. Researchers then simulate alcohol relapse by exposing the animals to stress, which causes them to again seek alcohol by lever-pressing. Stress in rats is reliably induced by injections of yohimbine, a drug that causes anxiety and panic. Using this approach, Dr. Heilig and colleagues from the NIAAA Laboratory of Clinical and Translational Studies found that by injecting rats with NPY, they could suppress the relapse-like alcohol-seeking behavior brought on by yohimbine. The findings, they note, support further study of NPY as a potential treatment for alcoholism.
Neurokinin-1 receptors (NK1R) are highly expressed in brain areas involved in stress responses and drug reward. In recent years, mounting research evidence has suggested that they may help regulate important aspects of alcohol use. In a new study, researchers at the NIAAA report that a compound that blocks NK1R suppresses alcohol drinking in mice. NIAAA Clinical Director Markus Heilig, M.D., Ph.D., and colleagues from the NIAAA Laboratory of Clinical and Translational Studies also showed that mice that lack the gene for NK1R have a lower preference for alcohol than do normal mice, and score lower on measures of alcohol reward, a key aspect of its addictive effects. Taken together, the data from the new study supports further investigation of NK1R blockade as a potential treatment for alcoholism.