Showing posts with label neuroplasticity. Show all posts
Showing posts with label neuroplasticity. Show all posts

Thursday, January 16, 2014

What is This Thing Called Neuroplasticity?


And how does it impact addiction and recovery?

Bielefeld, Germany—
The first in an irregular series of posts about a recent conference, Neuroplasticity in Substance Addiction and Recovery: From Genes to Culture and Back Again. The conference, held at the Center for Interdisciplinary Research (ZiF) at Bielefeld University, drew neuroscientists, historians, psychologists, philosophers, and even a freelance science journalist or two, coming in from Germany, the U.S., The Netherlands, the UK, Finland, France, Italy, Australia, and elsewhere. The organizing idea was to focus on how changes in the brain impact addiction and recovery, and what that says about the interaction of genes and culture. The conference co-organizers were Jason Clark and Saskia Nagel of the Institute of Cognitive Science at the University of Osnabrück, Germany.

One of the stated missions of the conference at Bielefeld’s Center for Interdisciplinary Research was to confront the leaky battleship called the disease model of addiction. Is it the name that needs changing, or the entire concept? Is addiction “hardwired,” or do things like learning and memory and choice and environmental circumstance play commanding roles that have been lost in the excitement over the latest fMRI scan?

What exactly is this neuroplasticity the conference was investigating? From a technical point of view, it refers to the brain’s ability to form new neural connections in response to illness, injury, or new environmental situations, just to name three. Nerve cells engage in a bit of conjuring known as “axonal sprouting,” which can include rerouting new connections around damaged axons. Alternatively, connections are pruned or reduced. Neuroplasticity is not an unmitigated blessing. Consider intrusive tinnitus, a loud and continuous ringing or hissing in the ears, which is thought to be the result of the rewiring of brain cells involved in the processing of sound, rather than the sole result of injury to cochlear hair cells.

The fact that the brain is malleable is not a new idea, to be sure. Psychologist Vaughn Bell, writing at Mind Hacks, has listed a number of scientific papers, from as early as 1896, which discuss the possibility of neural regeneration. But there is a problem with neuroplasticity, writes Bell, and it is that “there is no accepted scientific definition for the term, and, in its broad sense, it means nothing more than ‘something in the brain has changed.’” Bell quotes the introduction to the science text, Toward a Theory of Neuroplasticity: “While many scientists use the word neuroplasticity as an umbrella term, it means different things to different researchers in different subfields… In brief, a mutually agreed upon framework does not appear to exist.”

So the conference was dealing with two very slippery semantic concepts when it linked neuroplasticity and addiction. There were discussions of the epistemology of addiction, and at least one reference to Foucault, and plenty of arguments about dopamine, to keep things properly interdisciplinary. “Talking about ‘neuroscience,’” said Robert Malenka of Stanford University’s Institute for Neuro-Innovation and Translational Neurosciences, “is like talking about ‘art.’”

What do we really know about synaptic restructuring, or “brains in the wild,” as anthropologist Daniel Lende of the University of South Florida characterized it during his presentation? Lende, who called for using both neurobiology and ethnography in investigative research, said that more empirical work was needed if we are to better understand addiction “outside of clinical and laboratory settings.” Indeed, the prevailing conference notion was to open this discussion outwards, to include plasticity in all its ramifications—neural, medical psychological, sociological, and legal—including, as well, the ethical issues surrounding addiction.

Among the addiction treatment modalities discussed in conference presentations were optogenetics, deep brain stimulation, psychedelic drugs, moderation, and cognitive therapies modeled after systems used to treat various obsessive-compulsive disorders. Some treatment approaches, such as optogenetics and deep brain stimulation, “have the potential to challenge previous notions of permanence and changeability, with enormous implications for legal strategies, treatment, stigmatization, and addicts’ conceptions of themselves,” in the words of Clark and Nagel.

Interestingly, there was little discussion of anti-craving medications, like naltrexone for alcohol and methadone for heroin. Nor was the standard “Minnesota Model” of 12 Step treatment much in evidence during the presentations oriented toward treatment. The emphasis was on future treatments, which was understandable, given that almost no one is satisfied with treatment as it is now generally offered. (There was also a running discussion of the extent to which America’s botched health care system and associated insurance companies have screwed up the addiction treatment landscape for everybody.)

It sometimes seems as if the more we study addiction, the farther it slips from our grasp, receding as we advance. Certainly health workers of every stripe, in every field from cancer to infectious diseases to mental health disorders, have despaired about their understanding of the terrain of the disorder they were studying. But even the term addiction is now officially under fire. The DSM5 has banished the word from its pages, for starters.

Developmental psychologist Reinout Wiers of the University of Amsterdam used a common metaphor, the rider on an unruly horse, to stand in for the bewildering clash of top-down and bottom-up neural processes that underlie addictive behaviors. The impulsive horse and the reflective rider must come to terms, without entering into a mutually destructive spiral of negative behavior patterns. Not an easy task.

Monday, January 2, 2012

A Few Words About Glutamate


Meet another major player in the biology of addiction.

The workhorse neurotransmitter glutamate, made from glutamine, the brain’s most abundant amino acid, has always been a tempting target for new drug development. Drugs that play off receptors for glutamate are already available, and more are in the pipeline. Drug companies have been working on new glutamate-modulating antianxiety drugs, and a glutamate-active drug called acamprosate, which works by occupying sites on glutamate (NMDA) receptors, has found limited use as a drug for alcohol withdrawal after dozens of clinical trials.

Glutamine detoxifies ammonia and combats hypoglycemia, among other things. It is also involved in carrying messages to brain regions involved with memory and learning. An excess of glutamine can cause neural damage and cell death, and it is a prime culprit in ALS, known as Lou Gehrig’s disease. In sodium salt form, as pictured---> it is monosodium glutamate, a potent food additive. About half of the brain’s neurons are glutamate-generating neurons. Glutamate receptors are dense in the prefrontal cortex, indicating an involvement with higher thought processes like reasoning and risk assessment. Drugs that boost glutamate levels in the brain can cause seizures. Glutamate does most of the damage when people have strokes.

The receptor for glutamate is called the N-methyl-D-aspartate (NMDA) receptor. Unfortunately, NMDA antagonists, which might have proven to be potent anti-craving drugs, cannot be used because they induce psychosis. (Dissociative drugs like PCP and ketamine are glutamate antagonists.) Dextromethorphan, the compound found in cough medicines like Robitussin and Romilar, is also a weak glutamate inhibitor. In overdose, it can induce psychotic states similar to those produced by PCP and ketamine. Ely Lilly and others have looked into glutamate-modulating antianxiety drugs, which might also serve as effective anti-craving medications for abstinent drug and alcohol addicts.

As Jason Socrates Bardi at the Scripps Research Institute writes: "Consumption of even small amounts of alcohol increases the amount of dopamine in the nucleus accumbens area of the brain—one of the so-called ‘reward centers.’ However, it is most likely that the GABA and glutamate receptors in some of the reward centers of the basal forebrain—particularly the nucleus accumbens and the amygdala—create a system of positive reinforcement.”

Glutamate receptors, then, are the “hidden” receptors that compliment dopamine and serotonin to produce the classic “buzz” of alcohol, and to varying degrees, other addictive drugs as well. Glutamate receptors in the hippocampus may also be involved in the memory of the buzz.


Writing in The Scientist in 2002, Tom Hollon made the argument that “glutamate's role in cocaine dependence is even more central than dopamine's.” Knockout mice lacking the glutamate receptor mGluR5, engineered at GlaxoSmithKline, proved indifferent to cocaine in a study published in Nature.

In an article for Neuropsychology in 2009, Peter Kalivas of the Medical University of South Carolina and coworkers further refined the notion of glutamine-related addictive triggers: "Cortico-striatal glutamate transmission has been implicated in both the initiation and expression of addiction related behaviors, such as locomotor sensitization and drug-seeking," Kalivas writes. "While glutamate transmission onto dopamine cells in the ventral tegmental area undergoes transient plasticity important for establishing addiction-related behaviors, glutamatergic plasticity in the nucleus accumbens is critical for the expression of these behaviors."

The same year, in Nature Reviews: Neuroscience, Kalivas laid out his “glutamate homeostasis hypothesis of addiction.”

A failure of the prefrontal cortex to control drug-seeking behaviors can be linked to an enduring imbalance between synaptic and non-synaptic glutamate, termed glutamate homeostasis. The imbalance in glutamate homeostasis engenders changes in neuroplasticity that impair communication between the prefrontal cortex and the nucleus accumbens. Some of these pathological changes are amenable to new glutamate- and neuroplasticity-based pharmacotherapies for treating addiction.

This kind of research has at least a chance of leading in the direction of additional candidates for anti-craving drugs, without which many addicts are never going to successfully treat their disease.


Graphics credit: http://cnunitedasia.en.made-in-china.com/
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