Chapter 4. The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
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By PAULINE W. CHEN, M.D. Recounting her father’s struggle with cancer was difficult for the young woman, even several years after his death. He’d endured first surgery and then chemotherapy and radiation, she told me, and the cancer had gone into remission. He was thrilled, but the aggressive treatment left him with chronic, debilitating pain. Once active, he struggled to get around in his own home. “It wasn’t the cancer that got him,” the daughter said. “It was the pain.” Her father had turned to all of his doctors, with little relief. His surgeon had looked at his operative wounds, pronounced them well healed, then stated that they were in no way responsible for his disability. Both his cancer doctor and his radiation doctor congratulated him on being in remission but then declined to prescribe pain medications since they were no longer treating him and couldn’t provide ongoing follow-up and dosing guidance. His primary care doctor listened intently to his descriptions of his limitations, but then prescribed only small amounts of pain meds that offered fleeting relief at best. “I’ll never forget what my father had to go through,” she said, weeping. “I wouldn’t wish this on anyone.” I wish I could have reassured her that her father’s case was unusual. Sadly, according to a new study in The Journal of Clinical Oncology, a significant percentage of cancer patients continue to suffer from pain as her father did. Copyright 2012 The New York Times Company
By Janet Raloff Most people would never equate downing a well-dressed salad or a fried chicken thigh with toking a joint of marijuana. But to Joseph Hibbeln of the National Institutes of Health, the comparison isn’t a big stretch. New animal experiments by Hibbeln and his colleagues have recently shown that the body uses a major constituent in most vegetable oils to make its own versions of the psychoactive ingredient in marijuana. Called endocannabinoids, these natural compounds play a role in heightening appetite. So overproducing them unnecessarily boosts hunger, similarly to how pot triggers the munchies (SN: 6/19/10, p. 16). If what happens in people mirrors what happens in animals, then the prevalence of soybean oil, corn oil and other polyunsaturated vegetable oils in today’s Western diet means your body is “dumping out a lot of these marijuana-like molecules into your brain,” explains Hibbeln, a nutritional neuroscientist. “You’re chronically a little bit stoned.” Vegetable oil’s link to endocannabinoids is just one example of newfound and surprising ways that foods can confuse calorie-sensing networks and foster obesity — in some cases by damaging the brain. Especially troubling: Excess body weight itself can exaggerate the risk of the brain telling a well-fueled body that it is running on empty. By understanding what messes with the body’s satiety meters and why, scientists hope to identify tactics for reducing a diner’s likelihood of becoming another statistic in the obesity epidemic. © Society for Science & the Public 2000 - 2012
By Laura Sanders A dose of Ritalin makes healthy women more reckless in a gambling game. After taking the stimulant, participants in an experiment shifted their betting strategy and kept playing even when faced with stakes too high for most folks. Though solid numbers are scarce, evidence suggests that many healthy people turn to Ritalin (also known as methylphenidate) and other stimulants to boost mental capacity. Some college students, for instance, rely on these “smart pills” to focus attention in cram sessions before tests. The new results, published in the Sept. 19 Journal of Neuroscience, suggest that the drugs might have unanticipated consequences for these people, says study coauthor Daniel Campbell-Meiklejohn of New York University. Scientists have known that the very same drug has an opposite effect in people with attention deficit hyperactivity disorder and a kind of dementia, normalizing these people’s risky behavior. Scientists can’t yet explain Ritalin’s divergent effects, but they suspect that variations in how the brain handles the chemical messenger dopamine may be involved. Researchers enlisted 40 healthy women to take either Ritalin or a placebo, and later play a gambling game. The game was rigged so that the players would quickly rack up a loss and then have to choose whether to double-down in the hopes of recovering their money. “That’s the sad part of the game,” says Campbell-Meiklejohn, who conducted the study while at Aarhus University in Denmark. “You really can’t win.” © Society for Science & the Public 2000 - 2012
2012 by Graham Lawton My usual pick-me-up on a Monday morning is a cup of coffee. Today it's going to be something very different. I've been up since 6 am. I've had a breath test for alcohol, a urine test for drugs and a psychological test for mental health. Then I'm handed a red pill and a glass of water. I swallow it… and I'm told to relax. Which is easier said than done when you don't know if you've just taken vitamin C or 83 milligrams of pure MDMA. Half an hour later I'm inside an fMRI brain scanner, my head clamped in place and a visor over my face. It's noisy and claustrophobic but I'm reassured by the panic button in my hand and a voice from the control room. And then I start to feel it. A tingle of energy, like pins and needles, starts in the pit of my stomach and rises slowly, not unpleasant but not exactly pleasurable either. It builds in intensity, then breaks into a wave of bliss. The placebo effect can be powerful but when it happens again, I'm in no doubt. I'm coming up. I'm taking part in a groundbreaking study on MDMA, the drug commonly known as ecstasy. The research is run by David Nutt of Imperial College London, a former government adviser and one of the few UK researchers licensed to study class-A drugsMovie Camera. His main aim is to discover what MDMA does to the human brain, something that, remarkably, has never been done before. A second goal is to study MDMA as a therapy for post-traumatic stress disorder. © Copyright Reed Business Information Ltd
Excerpted from The Chemistry Between Us: Love, Sex and the Science of Attraction, by Larry Young, PhD, and Brian Alexander, by arrangement with Current, a member of Penguin Group (USA), Inc., Copyright © Larry J. Young and Brian Alexander, 2012. To investigate the rodent version of getting hugs, and what happens in the absence of hugs from a bonded partner, Bosch took virgin males and set them up in vole apartments with roommates—either a brother they hadn't seen in a long time or an unfamiliar virgin female. As males and females are wont to do, the boy-girl roommates mated and formed a bond. After five days, he split up half the brother pairs, and half the male-female pairs, creating what amounted to involuntary vole divorce. Then he put the voles through a series of behavioral tests. The first is called the forced-swim test. Bosch likens it to an old Bavarian proverb about two mice who fall into a bucket of milk. One mouse does nothing and drowns. The other tries to swim so furiously the milk turns into butter and the mouse escapes. Paddling is typically what rodents will do if they find themselves in water; they'll swim like crazy because they think they'll drown if they don't. (Actually, they'll float but apparently no rodent floaters have ever returned to fill in the rest of the tribe.) The voles that were separated from their brothers paddled manically. So did the voles who stayed with their brothers and the voles who stayed with their female mates. Only the males who'd gone through vole divorce floated listlessly as if they didn't care whether they drowned. "It was amazing," Bosch recalls. "For minutes, they would just float. You can watch the video and without knowing which group they were in, you can easily tell if it's an animal separated from their partner, or still with their partner." Watching the videos of them bob limply, it's easy to imagine them moaning out "Ain't No Sunshine When She's Gone" with their tiny vole voices. © 2012 Scientific American,
Keyword: Sexual Behavior
Link ID: 17257 - Posted: 09.15.2012
by Douglas Heaven The versatile cannabis plant may have a new use: it could be used to control epileptic seizures with fewer side effects than currently prescribed anti-convulsants. Ben Whalley at the University of Reading, UK, and colleagues worked with GW Pharmaceuticals in Wiltshire, UK, to investigate the anti-convulsant properties of cannabidivarin (CBDV), a little-studied chemical found in cannabis and some other plants. There is "big, historical, anecdotal evidence" that cannabinoids can be used to control human seizures, says Whalley, but the "side-effect baggage" means there have been relatively few studies of its pharmaceutical effect on this condition. The team investigated the effectiveness of CBDV – one of around 100 non-psychoactive cannabinoids found in cannabis – as an anti-convulsant. They induced seizures in live rats and mice that had been given the drug. These animals experienced less severe seizures and lower mortality compared with animals given a placebo. The drug also had fewer side effects and was better tolerated than three of the most widely prescribed anticonvulsants. Epileptic seizures affect about one per cent of the population. Left uncontrolled, they can lead to depression, cognitive decline and death. If you control the seizures, says Whalley, "the chances of death drop away completely". The decision about whether to test the drug in humans will be made next year. © Copyright Reed Business Information Ltd
by Douglas Heaven Nanoparticles often meet a sticky end in the brain. In theory, the tiny structures could deliver therapeutic drugs to a brain tumour, but navigating the narrow, syrupy spaces between brain cells is difficult. A spot of lubrication could help. Justin Hanes at Johns Hopkins University in Baltimore, Maryland, was surprised to discover just how impermeable brain tissue is to nanoparticles. "It's very sticky stuff," he says, similar in adhesiveness to mucus, which protects parts of the body – such as the respiratory system – by trapping foreign particles. It was thought that the adhesiveness of brain tissue limited the size of particles that can smoothly spread through the brain. Signalling molecules, nutrients and waste products below 64 nanometres in diameter can pass through the tissue with relative ease, but larger nanoparticles – suitable for delivering a payload of drugs to a specific location in the brain – quickly get stuck. Now Hanes and his colleagues have doubled that size limit. They coated their nanoparticles with a densely-packed polymer shield, which lubricates their surface by preventing electrostatic and hydrophobic interactions with the surrounding tissue. "A nice hydrated shell around the particle prevents it from adhering to cells," says Hanes. Using this approach, they were able to observe the diffusion of nanoparticles 114 nanometres in diameter through live mouse brains and dissected human and rat brain tissue. Hanes believes the true upper size limit now lies somewhere between 114 nm and 200 nm. "Things were starting to slow down at 114," he says. © Copyright Reed Business Information Ltd.
Link ID: 17219 - Posted: 08.30.2012
by Hannah Krakauer The downside to cannabis use has been made clearer. The most detailed study yet of the drug's long-term effects shows that those who start a weed habit as teens enter middle age with an 8-point deficit in IQ compared to non-users. Evidence is growing that cannabis-based drugs can benefit health, but suspicions remain that persistent cannabis use from an early age can have a detrimental effect on cognition. Confirming those suspicions is tricky, though, since cognitive impairment observed later in life could have been present before the drug was first used. To get around the problem Madeline Meier at Duke University in Durham, North Carolina, and her colleagues have taken the long view. They used a detailed health study which followed 1000 people in Dunedin, New Zealand, from birth until age 38. The data allowed them to compare IQ tests taken by the participants at age 13 – before any of them began using cannabis – with the same participants' IQ scores as adults, in some cases after years of cannabis use. The study showed that those who developed the most persistent dependence on the drug showed the greatest subsequent decline in IQ, losing 6 points on average regardless of how early the habit began. Within that group, those who began taking the drug before their 18th birthday saw a subsequent decline in IQ of 8 points, on average. © Copyright Reed Business Information Ltd.
By Bruce Bower All too often, high school students have to decide whether to join in on gulping down booze with the cool kids or lighting up a cigarette with parking-lot rebels. A new study suggests that genetics plays a role in the likelihood that some teens will succumb to this kind of peer pressure. Adolescents generally report drinking and smoking a lot in schools with high levels of such behavior, and doing so relatively infrequently in schools with low levels of substance use. These trends were stronger in teens with two copies of a short version of a gene called 5HTT than peers with two long versions, sociologist Jonathan Daw of the University of Colorado Boulder reported August 18 at the American Sociological Association’s annual meeting in Denver. Teens who had inherited one long and one short gene reported rates of alcohol and cigarette use that fell in between those of the other two groups, regardless of how much substance use occurred at their schools, Daw and his colleagues found. The 5HTT gene helps regulate transmission of serotonin, a chemical messenger in the brain. Daw’s team likens teens with the two short versions of the gene to social chameleons, more likely to conform to smoking and drinking styles of students around them than teens with one or no short variants. “Our data suggest that, alongside many other influences on adolescent substance use, genetics partly underlie individuals’ susceptibility to peer smoking and drinking,” Daw says. © Society for Science & the Public 2000 - 2012
By Scicurious Or not. I so want to like press releases. But I got this press release: “SCIENTISTS CAN NOW BLOCK HEROIN, MORPHINE ADDICTION” And I got the paper along with it. As I read the paper, my head slowly hit the desk. And hit it again, and again, as I compared the press release to the paper and prepared to write this post. I will have a lovely little round bruise now. But let’s get the big questions out of the way first: 1. Is this paper good? Oh yes! Really neat! Cool new mechanism! 2. Does it “block” heroin addiction? No. This press release hurts us precious. It hurts us. This paper has a lot of GREAT things about it, and there’s a lot of potential for the future with a new mechanism for drug action, especially in the area of pain relief (which sadly got short shrift in the press release). But no one has cured addiction yet. © 2012 Scientific American
by Catherine de Lange A potential new treatment to prevent morphine addiction is at hand. Researchers have identified an immune receptor involved in addiction to the drug, and found a way to block this receptor without affecting pain relief. The discovery offers hope that morphine can be used to relieve pain without running the risk of addiction. Opioid drugs such as morphine are known to target opioid receptors in the central nervous system, which block pain signals to the brain and flood it with the "feel-good" chemical dopamine. This reward response is what makes opioids so addictive. Morphine is a widely used pain killer, but its addictiveness means it has to be administered with caution, and often cannot be used for protracted periods of chronic pain. Mark Hutchinson from the University of Adelaide, Australia, and colleagues have now discovered that as well as working through the central nervous system, opioid drugs like heroin and morphine trigger an immune response, which seems to boost their addictive effects. Blocking this immune response in animals inhibits their addiction. Hutchinson's team previously observed that opioids bind to TLR-4 – immune system receptors in the cell membrane – which are responsible for identifying foreign bodies. However, the team did not know how this binding affected the body. © Copyright Reed Business Information Ltd.
By Karen Weintraub Dr. Steven E. Hyman, a neuroscientist and former Harvard provost, now directs the Stanley Center for Psychiatric Research at the Broad Institute, which is trying to better understand and develop treatments for conditions like depression, anxiety, schizophrenia, bipolar disorder, ADHD, obsessive-compulsive disorder, and autism. Q. There haven’t been a lot of drugs developed recently to treat these conditions. A. The modern era of neuropsychopharmacology began brilliantly in the early 1950s. There has been enormous progress in making drugs safer and more tolerable. [But effectiveness has not improved substantially.] We’ve reached a fairly unsatisfactory place in the treatment of these devastating illnesses. Q. Big drug companies are now getting out of the business of developing new medications for these conditions. A. The pharmaceutical industry is basically giving up and throwing in the towel. Their exit is both a symptom of the difficulty and a problem. Q. What does this mean for someone with one of these conditions? A. I don’t want to be inappropriately negative. If somebody has OCD or panic disorder or depression, the combination of cognitive behavioral therapy and a well chosen SSRI-like drug [like Prozac] will, for a reasonable fraction of those patients, markedly improve their lives, although there will be side effects and residual symptoms. © 2012 NY Times Co.
COFFEE can give you the shakes, but caffeine seems to have the opposite effect in people with Parkinson's disease, helping to relieve tremors and get them back on the move. In the past, caffeine has been shown to reduce the risk of Parkinson's, but its effects have never been tested in people who already have the disease. Ronald Postuma of McGill University in Montreal, Canada, and colleagues gave 61 people with Parkinson's a 6-week course of pills containing the caffeine equivalent of about three cups of coffee every day, or a placebo. Only people in the caffeine group showed a significant improvement in tests for motor problems, such as the severity of their tremors, and general mobility (Neurology, DOI: 10.1212/WNL.0b013e318263570d). Motor problems associated with Parkinson's are caused by a lack of dopamine in areas of the brain where dopamine-producing cells are destroyed. Adenosine receptors normally inhibit the production of dopamine. Caffeine blocks adenosine receptors and so acts to boost available dopamine. Drugs that target adenosine receptors are already in clinical trials but caffeine could provide a cheaper alternative. © Copyright Reed Business Information Ltd.
Link ID: 17123 - Posted: 08.04.2012
by Kai Kupferschmidt Tabloid journalists have long known that you can discover dirty secrets by going through people's garbage. Now, researchers have done something similar in the name of science, albeit on a grander—and smellier—scale. They have analyzed the sewage of 19 European cities to find out how much of certain illicit drugs people in those cities consume. "The technique needs further work and validation, but this paper shows that it is a feasible approach for estimating drug use on a large scale," says Fritz Sörgel, head of the Institute for Biomedical and Pharmaceutical Research in Nuremberg, Germany, who was not involved in the work. To put figures on illicit drug use, researchers routinely use surveys, supplemented by data from police and customs. But they have been pushing for more accurate and objective methods to estimate the amounts consumed. One possibility is to sample the sewage of a city and look for chemical traces of the drugs themselves or metabolites created when a drug passes through the human body. "The surveys tell you what people take, but not how much, not how big the market is," says Kevin Thomas, a toxicologist at the Norwegian Institute for Water Research in Oslo and one of the authors of the new paper. "Sewage tells you that." During one week in March 2011, Thomas and colleagues collected daily samples representing 24 hours of sewage flow from 21 sewage treatment plants in 19 cities across Europe—from Antwerp to Zagreb. The samples were analyzed for traces of five different drugs by local labs according to a fixed protocol. © 2010 American Association for the Advancement of Science.
Keyword: Drug Abuse
Link ID: 17104 - Posted: 07.30.2012
By Laura Sanders Light use of the club drug Ecstasy may cause subtle memory deficits. People who popped just three Ecstasy tablets a month over the course of a year saw their memory slip on a laboratory test, scientists report online July 25 in Addiction. The new results offer some of the best evidence yet that the drug can change the brain, says psychiatric neuroscientist Ronald Cowan of Vanderbilt University Medical Center in Nashville. “It’s been very, very difficult to convince people that there’s a causative effect of the drug,” he says. “This adds strong evidence to that.” Scientists debate whether Ecstasy, a drug that brings euphoria, boundless energy and heightened sensory experiences, can actually harm the brain in part by screwing with cells that produce the chemical messenger serotonin. Past studies have been notoriously hard to interpret because brain differences seen between Ecstasy users and nonusers could have existed long before the drug use began. And people who use Ecstasy frequently tend to use other drugs too, making it hard to tease out Ecstasy’s effect. For the study, Daniel Wagner of the University of Cologne in Germany and his colleagues wanted to catch people as they started using Ecstasy. The team recruited 149 people who had used Ecstasy five or fewer times and ran the subjects through a battery of brain tests looking for signs of mental deficits. One year later, the team retested 43 people who had not used Ecstasy since being recruited, and 23 who had used 10 or more Ecstasy pills in that time. These people reported using an average of 33.6 tablets. © Society for Science & the Public 2000 - 2012
Most children exposed to high levels of alcohol in the womb do not develop the distinct facial features seen in fetal alcohol syndrome, but instead show signs of abnormal intellectual or behavioral development, according to a study by researchers at the National Institutes of Health and researchers in Chile. These abnormalities of the nervous system involved language delays, hyperactivity, attention deficits or intellectual delays. The researchers used the term s functional neurologic impairment to describe these abnormalities. The study authors documented an abnormality in one of these areas in about 44 percent of children whose mothers drank four or more drinks per day during pregnancy. In contrast, abnormal facial features were present in about 17 percent of alcohol exposed children. Fetal alcohol syndrome refers to a pattern of birth defects found in children of mothers who consumed alcohol during pregnancy. These involve a characteristic pattern of facial abnormalities, growth retardation, and brain damage. Neurological and physical differences seen in children exposed to alcohol prenatally — but who do not have the full pattern of birth defects seen in fetal alcohol syndrome — are classified as fetal alcohol spectrum disorders. “Our concern is that in the absence of the distinctive facial features, health care providers evaluating children with any of these functional neurological impairments might miss their history of fetal alcohol exposure,” said Devon Kuehn, M.D., of the Epidemiology Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH institute involved in the study. “As a result, children might not be referred for appropriate treatment and services.” Their findings appear online in Alcoholism: Clinical and Experimental Research.
By Scicurious Ah, coffee, the beautiful stimulant without which about 90% of science and medicine would instantly retreat to the dark ages. Seriously, who hasn’t needed that extra cup of joe (or two, or three) to make it through another 14 hour experimental day, a 10 hour surgery, or, you know, both? But our favorite adenosine antagonist has a downside. Too much caffeine and you can get a racing heartbeat, nerves, and a certain amount of palm sweat, not to mention problems when you try to sleep at night. But all of that is just yourself. Does caffeine affect the way you view other people? Well, if you’re getting a little anxious, yes, it does. Caffeine does act the way other stimulants do. Instead of acting on neurotransmitters like dopamine or norepinephrine, caffeine acts on adenosine. Adenosine is another neurotransmitter, this one associated with things like sleepiness. High levels of adenosine promote sleepiness, and low levels promote wakefulness. Caffeine acts on the adenosine receptor as an antagonist, meaning that it blocks the effects of adenosine, promoting wakefulness. But wakefulness and sleepiness are not all that adenosine does. Adenosine and adenosine receptors have been implicated in things like anxiety disorders. This could be particularly important when these receptors are expressed in the amygdala, medial prefrontal cortex, and periaqueductal grey, areas of the brain associated with things like fear processing and anxiety. And of course, if adenosine receptors are there, and caffeine is there, too, you might be getting some effects of caffeine on processing in these areas. © 2012 Scientific American
By Janet Raloff A resin in the most commonly used white composite dental fillings may be linked to subtle neuropsychological deficits in children. The association appears in reanalyzed data collected from 434 children as part of a trial begun roughly a decade ago. The original study was designed to probe for IQ or other neurobehavioral impacts of the mercury that can be released by metal-amalgam dental fillings. Half of the kids received amalgam fillings for cavities in back teeth, the rest got composite back fillings. Cavities in front teeth always got composite fillings. Wherever composites were used, baby teeth got a urethane-based resin, while permanent teeth got a resin called bis-GMA that is derived from bisphenol A, or BPA. BPA can mimic the hormonal activity of estrogen and exposure in the womb has been linked to behavioral changes in mice and young children. The 6- to 10-year olds were then followed for five years, with the children or their parents periodically participating in assessments of a kid’s mood, behaviors (including aggression), attitudes at school and interpersonal relationships. That original study, published in 2006, turned up no problems associated with metal fillings. But the research did hint that composite fillings might be worrisome. After reanalyzing their data, the researchers now find that children receiving bis-GMA fillings did exhibit low-level changes on behavioral assessments. © Society for Science & the Public 2000 - 2012
By Ruth Williams Until recently, most scientists believed that neurons were the all-important brain cells controlling mental functions and that the surrounding glial cells were little more than neuron supporters and “glue.” Now research published in March in Cell reveals that astrocytes, a type of glia, have a principal role in working memory. And the scientists made the discovery by getting mice stoned. Marijuana impairs working memory—the short-term memory we use to hold on to and process thoughts. Think of the classic stoner who, midsentence, forgets the point he was making. Although such stupor might give recreational users the giggles, people using the drug for medical reasons might prefer to maintain their cognitive capacity. To study how marijuana impairs working memory, Giovanni Marsicano of the University of Bordeaux in France and his colleagues removed cannabinoid receptors—proteins that respond to marijuana's psychoactive ingredient THC—from neurons in mice. These mice, it turned out, were just as forgetful as regular mice when given THC: they were equally poor at memorizing the position of a hidden platform in a water pool. When the receptors were removed from astrocytes, however, the mice could find the platform just fine while on THC. The results suggest that the role of glia in mental activity has been overlooked. Although research in recent years has revealed that glia are implicated in many unconscious processes and diseases, this is one of the first studies to suggest that glia play a key role in conscious thought. “It's very likely that astrocytes have many more functions than we thought,” Marsicano says. “Certainly their role in cognition is now being revealed.” © 2012 Scientific American,
Many people who abused the painkiller OxyContin by inhaling or injecting it switched to heroin after the prescription's formula changed, U.S. researchers say. OxyContin was designed to slowly release the opioid drug oxycodone. After people started abusing it by crushing the pills and inhaling the powder or dissolving the pills in water and injecting it to get a rush, the drug maker introduced a new formula in the U.S. in 2010 to make inhaling and injecting more difficult. The new pills are harder to crush and dissolve more slowly. In Wednesday's issue of the New England Journal of Medicine, investigators in the U.S. said use of OxyContin by inhalation and injection has dropped significantly since the abuse-deterrent form went on the market. "In that sense, the new formulation was very successful," said author and principal investigator Theodore Cicero, a professor of neuropharmacology in psychiatry at Washington University School of Medicine in St. Louis, Mo. "The most unexpected, and probably detrimental, effect of the abuse-deterrent formulation was that it contributed to a huge surge in the use of heroin," he added in a release. OxyContin was a popular drug in suburban and urban areas, where drug abusers have now shifted either to more potent opioids if they can find them or to heroin, he said. © CBC 2012
Keyword: Drug Abuse
Link ID: 17028 - Posted: 07.12.2012