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In mice, alcohol dependence results in brain-wide remodeling of functional architecture -- ScienceDaily

"The neuroscience of addiction has made tremendous progress, but the focus has always been on a limited number of brain circuits and neurotransmitters, primarily dopaminergic neurons, the amygdala and the prefrontal cortex," said senior author Olivier George, PhD, associate professor in the Department of Psychiatry at UC San Diego School of Medicine. "Research groups have been fighting for years about whether 'their' brain circuit is the key to addiction. Our results confirm these regions are important, but the fact that we see such a massive remodeling of the functional brain architecture was a real shock. It's like studying the solar system and then discovering that there is an entire universe behind it. It shows that if you really want to understand the neurobiological mechanisms leading to addiction, you can't just look at a handful of brain regions, you need to look at the entire brain, you need to take a step back and consider the whole organ." George said the findings further undermine the idea that addiction is simply a psychological condition or consequence of lifestyle. "You would be surprised at how prevalent this view remains," he said. "The brain-wide remodeling of the functional architecture observed here is not 'normal.' It is not observed in a naïve animal. It is not observed in an animal that drinks recreationally. It is only observed in animals with a history of alcohol dependence and it is massive. Such a decrease in brain modularity has been observed in numerous brain disorders, including Alzheimer's disease, traumatic brain injury and seizure disorders." Brain modularity is the theory that there are functionally specialized regions in the brain responsible for different, specific cognitive processes. For example, the frontal lobes of the human brain are involved in executive functions, such as reasoning and planning, while the fusiform face area located in the lower rear of the brain is involved in recognizing faces. Reduced modularity, said George, likely interferes with "normal neuronal activity and information processing and contributes to cognitive impairment, emotional distress and intense craving observed in mice during abstinence from alcohol." Due to the format of the testing, George said it was not clear if the reduced modularity was permanent. "So far, we only know that it lasts at least one week into abstinence. We have not tested longer durations of abstinence, but it's one of our goals."

The Art of Dying | The New Yorker

I was climbing stairs and paused, too exhausted for another step. I harbored a nebulous conviction that I could tolerate only so much pain, short of a red zone in which I would go mad or die or something terrible would happen. And that anyone should see as much and want me to do anything—have a drink or a drug, for starters—to make it stop. I thought, They say one day at a time. How about one second? I stared at my ticking watch. A black abyss opened. I was numbly aware that I wasn’t insane. I wasn’t dying. Reality was droning on as usual, with impartial sunlight streaming through a nearby window and picking out swirls of dust motes. A perfectly demented thought blazed up. Roughly: What if they find out I’m not really an alcoholic and throw me out of here? I need this place! I believe it was the last, deepest rootlet of my denial, expelled. Not an alcoholic?

The Art of Dying | The New Yorker

See, Brooke is a child of alcoholics, as I’m not. I grew up and became one. She grew up and married one. She knew I was a mess but thought the drinking part was normal, until she got wise and kicked me out of the house. (Note to anyone who knows an active alcoholic: never, ever sympathize. If you suspect you’re going to, shut your eyes, plug your ears, and hum.)

The Art of Dying | The New Yorker

I remember, in rehab, on the Upper East Side in 1992, an alum of the place, a tough guy from Queens, addressing the nightly A.A. meeting. He told us of once showing up at some clinic, drunk and filthy and soiled with his own diarrhea, and throwing a fit because the doctor was ten minutes late. “If you’re a real alcoholic,” the guy said to us, “no matter how low you go, you will have an attitude.” He added, “If you’re a real alcoholic, you will never feel quite right. Whatever you want will be a little bit out of reach. Can’t handle that? Get the fuck out of here and get drunk.” I went up to him afterward, in tears, to thank him. He said, “You heard me?” I said yes. “Good,” he said, turning and walking away as if from some crap on a sidewalk. Saved my life.

What Chris said

I figuratively put all the chemicals in a funnel, and they came out bourbon. Jack Daniel’s-on-the-rocks, with a splash, except when scarce funds reduced me to Heaven Hill. Alcohol was liberating for me at first. A standard progression: great, good, fair, poor, bad, very bad, and then a phase for which any word but “Hell” fails. Halfway through the second drink, there may be a flicker of the old euphoria, quickly snuffed. You chase it in vain for the rest of a wretched night. It’s over for you. A line has been crossed. Yet you cannot imagine yourself not drinking. The obsession is at one with your core sense of self.

Cycles of reward: New insight into ADHD treatment: Neural processes involved in ADHD -- ScienceDaily

Neurons release dopamine in different ways: phasic release is characterized by quick, high intensity spikes in the neurotransmitter, often in response to motivational stimuli like drugs or sugary treats. Tonic release, on the other hand, refers to slower, more regular firings of dopamine neurons, and is involved in muscle and joint movements. Wickens and his collaborators initially thought that, since methylphenidate blocks the reuptake of dopamine by receptors in the brain, that the drug should increase the phasic dopamine signal. Rather, after analyzing their data, the researchers found the opposite: methylphenidate did not increase phasic dopamine. To explain this finding, Wickens suspects that the brain has a remarkably powerful feedback mechanism to keep the brain's dopamine levels in check, even when reuptake is blocked by methyphenidate. "When you use methylphenidate in the intact brain there's a neural regulation mechanism to compensate for the direct effects of the drug," said Wickens. "Methylphenidate's therapeutic effects could be indirect consequences of this feedback loop." The computer modeling suggests that methylphenidate primarily impacts the tonic dopamine signal. Shifts in tonic dopamine signaling may activate dopamine receptors in ways that improve the symptoms of ADHD.

Consuming alcohol leads to epigenetic changes in brain memory centers -- ScienceDaily

n, in mouse models, how acetate -- a byproduct of the alcohol breakdown produced mostly in the liver -- travels to the brain's learning system and directly alters proteins that regulate DNA function. This impacts how some genes are expressed and ultimately affects how mice behave when given environmental cues to consume alcohol. Their findings were published today in Nature. "It was a huge surprise to us that metabolized alcohol is directly used by the body to add chemicals called acetyl groups to the proteins that package DNA, called histones," said the study's senior author Shelley Berger, PhD, the Daniel S. Och University Professor in the departments Cell and Developmental Biology and Biology, and director of the Penn Epigenetics Institute. "To our knowledge, this data provides the first empirical evidence indicating that a portion of acetate derived from alcohol metabolism directly influences epigenetic regulation in the brain."

Hub linking movement and motivation in brain identified -- ScienceDaily

lateral septum (LS), a region considered integral to modulating behavior and implicated in many psychiatric disorders, directly encodes information about the speed and acceleration of an animal as it navigates and learns how to obtain a reward in an environment. "Completing a simple task, such as acquiring food for dinner, requires the participation and coordination of a large number of regions of the brain, and the weighing of a number of factors: for example, how much effort is it to get food from the fridge versus a restaurant," said Hannah Wirtshafter, the study's lead author. "We have discovered that the LS may be aiding you in making some of those decisions. That the LS represents place, movement, and motivational information may enable the LS to help you integrate or optimize performance across considerations of place, speed, and other environmental signals."

How relapse happens: Opiates reduce the brain's ability to form, maintain synapses: Preclinical research was focused on revealing the molecular mechanisms behind addiction and relapse -- ScienceDaily

In experiments with rodents, the UB team determined that exposure to heroin and morphine reduced drebrin levels in the nucleus accumbens, a key part of the brain's reward pathway. Synaptic rewiring The researchers found that opiate exposure causes synaptic rewiring in this part of the brain, as well as a decrease in drenditic spines, the protrusions on neurons that play key roles in neuronal transmission, learning and memory. "Opiates fundamentally change how the brain communicates with itself," Dietz said.

Prizes for sobriety: As Washington meth use rises, this treatment is one of few that works | The Seattle Times

Here’s how the treatment works: You come in a few times a week, complete a urine test, and if it’s negative, you draw for a prize — at a trial McDonell is running in Wallingford, there are “small” prizes like shampoo or a toothbrush, “big” prizes like a coffeemaker, or rare “jumbo” prizes like a DVD player. The longer you’re sober, the more draws you get, but if the test comes back positive, the clinician says “see you next time.”

Mindful body awareness training during treatment for drug addiction helps prevent relapse -- ScienceDaily

The intervention is called Mindful Awareness in Body-oriented Therapy (MABT) and combines manual, mindfulness and psycho-educational approaches to teach interoceptive awareness and related self-care skills. Interoceptive awareness is the ability to access and process sensory information from the body. Researchers studied 187 women at three Seattle-area locations. The cohort, all women in treatment for substance use disorder (SUD), was split into three relatively equal groups. Every group continued with their regular SUD treatment. One group received SUD treatment only, another group was taught the mindfulness technique in addition to treatment, and the third group received a women's education curriculum in addition to treatment in order to test whether the additional time and attention explained any positive study outcomes. Women were tested at the beginning, and at three, six and 12 months on a number of factors including substance use, distress craving, emotion regulation (self-report and psychophysiology), mindfulness skills and interoceptive awareness. There were lasting improvements in these areas for those who received the MABT intervention, but not for the other two study groups. "Those who received MABT relapsed less," Price said. "By learning to attend to their bodies, they learned important skills for better self-care."

Want to quit smoking? Partner up: Couples who attempt to stop smoking together have a sixfold chance of success -- ScienceDaily

At the end of the programme, 64% of patients and 75% of partners were abstinent -- compared to none and 55% at the start, respectively. The odds of quitting smoking at 16 weeks were significantly higher (5.83-fold) in couples who tried to quit together compared to patients who attempted it alone. "Previous research has shown that ex-smokers can also positively influence their spouse's attempts to quit, but in this study the effect was not statistically significant," said Ms Lampridou. "As for non-smoking partners, there is a strong risk that they will adopt their spouse's habit." Ms Lampridou noted that research is needed to confirm the findings in smokers who are otherwise healthy.

ADHD drug Ritalin has no effect on primate prefrontal cortex -- ScienceDaily

Julio Martinez-Trujillo and colleagues refute their hypothesis the caudal prefrontal cortex -- a brain region critical for attention -- is Ritalin's main site of action in the brain. To arrive at this conclusion, the researchers recorded large populations of neurons in this brain region as two male macaque monkeys performed a demanding visual attention task. The team did not observe any differences in neuronal activity after administration of the drug compared to a placebo, even at doses that improved the monkeys' performance on the task.

Heavy drinking may change DNA, leading to increased craving for alcohol: Genetic vicious cycle may reinforce risky drinking behavior -- ScienceDaily

Scientists at Rutgers and Yale University School of Medicine focused on two genes implicated in the control of drinking behavior: PER2, which influences the body's biological clock, and POMC, which regulates our stress-response system. By comparing groups of moderate, binge and heavy drinkers, the researchers found that the two genes had changed in the binge and heavy drinkers through an alcohol-influenced gene modification process called methylation. The binge and heavy drinkers also showed reductions in gene expression, or the rate at which these genes create proteins. These changes increased with greater alcohol intake. Additionally, in an experiment, the drinkers viewed stress-related, neutral or alcohol-related images. They also were shown containers of beer and subsequently tasted beer, and their motivation to drink was evaluated. The result: alcohol-fueled changes in the genes of binge and heavy drinkers were associated with a greater desire for alcohol.

Exercise and memory mechanisms

Mice were given cocaine injections over four days in special chambers with a distinctive floor texture to produce a drug association with that environment. The animals were then housed for 30 days in cages, some of which included a running wheel. The researchers found that mice that exercised on these wheels had lower levels of brain peptides related to myelin, a substance that is thought to help fix memories in place. Re-exposure to the cocaine-associated environment affected running and sedentary mice differently: Compared with sedentary mice, the animals with running wheels showed a reduced preference for the cocaine-associated environment. In addition, the brains of re-exposed runners contained higher levels of hemoglobin-derived peptides, some of which are involved in cell signaling in the brain. Meanwhile, peptides derived from actin decreased in the brains of re-exposed sedentary mice. Actin is involved in learning and memory and is implicated in drug seeking. The researchers say these findings related to peptide changes will help to identify biomarkers for drug dependence and relapse.

Dopamine Drives Early Addiction to Heroin - Neuroscience News

To prove that increased dopamine directly causes drug reinforcement, the team looked at the effects of silencing dopamine in mice with a well-established heroin addiction and were consistently self-administering the drug using a lever. They found that when they silenced the dopamine neurons, the mice were much less likely to self-administer heroin. Crucially, when they did this early in the addiction phase, the mice were less likely to develop the habit of self-administering heroin. This showed that activation of dopamine neurons in the nucleus accumbens is required for the early positive reinforcing effects of opioid drugs.

Just a few drinks can change how memories are formed -- ScienceDaily

One of the downstream dominos in the signaling pathway affected by alcohol is a gene called dopamine-2-like receptor, which makes a protein on neurons that recognizes dopamine, the "feel-good" neurotransmitter. "The dopamine-2-like receptor is known to be involved in encoding whether a memory is pleasing or aversive," Petruccelli said. And alcohol hijacks this conserved memory pathway to form cravings. In the case of the alcohol reward pathway studied, the signaling cascade didn't turn the dopamine receptor gene on or off, or increase or decrease the amount of protein made, Kaun said. Instead, it had a subtler effect -- it changed the version of the protein made by a single amino acid "letter" in an important area. "We don't know what the biological consequences of that small change are, but one of the important findings from this study is that scientists need to look not only at which genes are being turned on and off, but which forms of each gene are getting turned on and off," Kaun said. "We think these results are highly likely to translate to other forms of addiction, but nobody has investigated that."

New target of alcohol in the brain -- ScienceDaily

"The KCNK13 channel is absolutely required for alcohol to stimulate the release of dopamine by these neurons," said Mark Brodie, professor of physiology and biophysics in the UIC College of Medicine and lead author of the study. "Without the channel, alcohol can't stimulate the release of dopamine, and so drinking is likely less rewarding. We think that the KCNK13 channel presents an extremely exciting new target for drugs that could potentially help people with alcohol use disorder to stop drinking."

Coping with Suicide - How to Deal When Someone Kills Themself

My mother expected something of me that no child could deliver: to never grow up and away from her. To adore her always and unconditionally. Mostly I realized that it wasn't one event that turned her from life to death, but a lifetime of circumstances that culminated in one fateful choice.

The Truth About Prescription Pills: One Writer's Story of Anxiety and Addiction — Vogue - Vogue

Like me, she wasn’t a vodka-in-the-morning drinker, but when she drank—usually California Chardonnays—she couldn’t stop. She’d get high and silly and then, at the drop of a dime, she’d turn mean, lashing out at those closest to her. It was so contrary to her fundamental nature—kind, compassionate, sensitive—and she hated herself for the times she hurt our family. But ultimately, no pill or drink, no amount of love, could soothe her sadness. When I was 22, she took her life. I worried that her suffering was a warning, a glimpse of what my future might be if I didn’t change things.

Inside Marijuana Anonymous, the group for people addicted to weed – VICE News

Michael described it as a silent addiction. “No one sees you, you’re not out robbing people. You’re not beating people up, you’re not getting into fights,” he said. “So for the rest of society, you’re not really a problem. You’re just a problem to yourself because you’re not doing anything with your life.” “It’s like being kicked to death by a bunny.” One of the reasons people might hold the view that cannabis is safer is because the withdrawal syndrome is kind of non-specific and could easily be attributed to something else, said Juurlink.

Can You Get Addicted to Pot? - The Atlantic

Public-health experts worry about the increasingly potent options available, and the striking number of constant users. “Cannabis is potentially a real public-health problem,” said Mark A. R. Kleiman, a professor of public policy at New York University. “It wasn’t obvious to me 25 years ago, when 9 percent of self-reported cannabis users over the last month reported daily or near-daily use. I always was prepared to say, ‘No, it’s not a very abusable drug. Nine percent of anybody will do something stupid.’ But that number is now [something like] 40 percent.”

Exercise Can Help Beat Cocaine Addiction - Neuroscience News

Using animal models, Thanos found that regular aerobic exercise (one hour on a treadmill, five times a week) decreased stress-induced cocaine-seeking behavior. Exercise also altered behavioral and physiological responses to stress. Individuals who are addicted to cocaine have altered neural, behavioral and physiological responses to stress. Recent research by Thanos demonstrated how exercise can alter the brain’s mesolimbic dopamine pathway, which is linked to the rewarding and reinforcing properties of drugs such as cocaine. In addition, exercise has been shown to reduce stress hormones and elevate mood, which could assist in alleviating anxiety and negative emotions associated with withdrawal.

ADHD drugs do not improve cognition in healthy college students -- ScienceDaily

Results of the new study, published last month in the journal Pharmacy, show that the standard 30 mg dose of Adderall did improve attention and focus -- a typical result from a stimulant -- but that effect failed to translate to better performance on a battery of neurocognitive tasks that measured short-term memory, reading comprehension and fluency. Weyandt has a theory about why working memory would be adversely affected by the medication. Brain scan research shows that a person with ADHD often has less neural activity in the regions of the brain that control executive function -- working memory, attention, self-control. For people with ADHD, Adderall and similar medications increase activity in those regions and appear to normalize functioning. "If your brain is functioning normally in those regions, the medication is unlikely to have a positive effect on cognition and my actually impair cognition. In other words, you need to have a deficit to benefit from the medicine," Weyandt said. Participants in the study also reported their perceived effects of the drug and its impact on their emotions, with students reporting significant elevation of their mood when taking Adderall. In contrast to the small, mixed effects on cognition, the drug had much larger effects on mood and bodily responses, increasing positive mood, emotional ratings of the drug effect, heart rate and blood pressure. "These are classic effects of psychostimulants," said White. "The fact that we see these effects on positive emotion and cardiovascular activity, in the same individuals for whom cognitive effects were small or negative in direction, is important. It indicates that the cognitive and the emotional impact of these drugs are separate. How you feel under the drug does not necessarily mean that there is an improvement in cognition; there can be a decrease, as seen here in young adults without ADHD."

Author hints at higher drug use (including prescriptions) then blames individualism

It is not clear what exactly drives the demand for the psychoactive substances and what has driven the increase in suicides. But I think it’s worth speculating whether a perceived low quality of life for many Americans, marked by high stress and low levels of happiness, is contributing. Americans stand out from people in other countries with respect to their focus on individualism. Americans believe that success is determined by our own control and that it is very important to work hard to get ahead in life. Perhaps it is this focus on our own achievements, successes and work culture that have created an environment that is no longer sustainable – it has become too stressful.

Exercise Reduces Dopamine D1R and Increases D2R in Rats: Implications for Addiction

Exercised rats had 18% and 21% lower D1R-like binding levels compared to sedentary rats within the olfactory tubercle (OT) and nucleus accumbens shell (AcbS), respectively. In addition, male and female exercise rats showed greater D2R-like binding levels within the dorsomedial (DM CPu; 30%), ventrolateral (VL CPu; 24%), and ventromedial (VM CPu; 27%) caudate putamen, as well as the OT (19%). Greater D2R-like binding in the nucleus accumbens core (AcbC; 24%) and shell (AcbS; 25%) of exercised rats compared to sedentary rats approached significance. No effects were found for DAT binding.