Tag Archives: dopamine

Pain impairs our ability to feel pleasure — and now we know why, and how

Researchers are homing in on the brain circuits that handle pain-induced anhedonia, the reduction in motivation associated with experiencing pain. The findings, currently only involving lab rats, might prove pivotal in our efforts to address depression and the rising issue of opioid addiction.

Pain is definitely not a sensation most of us are excited to experience. And although physical hurt is obviously unpleasant, it isn’t the only component of this sensation. Affective pain can be just as debilitating, and much more insidious. New research has identified the brain circuits that mediate this kind of pain, in a bid to counteract its long-term effects — which can contribute to the emergence of depression and make people vulnerable to addictions that take that pain away, such as opioid use disorder (OUD).

Show me where it hurts

Chronic pain is experienced on many levels beyond just the physical, and this research demonstrates the biological basis of affective pain. It is a powerful reminder that psychological phenomena such as affective pain are the result of biological processes,” said National Institute on Drug Abuse (NIDA) Director Nora D. Volkow, M.D, who was not affiliated with this study.

“It is exciting to see the beginnings of a path forward that may pave the way for treatment interventions that address the motivational and emotional effects of pain.”

Pain, the authors explain, has two components: a sensory one (the part you can feel) and an affective, or emotional, component. Anhedonia — an inability to feel pleasure and a loss of motivation to pursue pleasurable activities — is one of the central consequences of affective pain. Considering the strong links between anhedonia, depression, and substance abuse, the NIDA has a keen interest in understanding how our brains produce and handle affective pain.

Previous studies found that rats in pain were more likely to consume higher doses of heroin compared to their peers. In addition to this, they lost a sizable chunk of their motivation to seek out other sources of reward (pleasure), such as sugar tablets.

The current paper built on these findings, and aimed to see exactly how this process takes place in the brain. The team measured the activity of dopamine-responding neurons in a part of the brain’s “reward pathway” known as the ventral tegmental area. This activity was measured while the rats used a lever with their front paw to receive a sugar tablet. In order to see what effect pain would have on the activity of these neurons, rats in the experimental group received an injection that produced local inflammation in their hind paw. Rats in the control group were injected with saline solution.

After 48 hours, the researchers noted that rats in the experimental group pressed the lever less than their peers, indicative of a loss of motivation. They also saw lower activity levels in their dopamine neurons. Further investigations revealed that these neurons were less active because the sensation of pain was activating cells from another region of the brain known as the rostromedial tegmental nucleus (RMTg). Neurons in the RMTg are, among other tasks, responsible for producing the neurotransmitter GABA, which inhibits the functions of dopamine neurons.

Despite this, when the authors artificially restored functionality to the dopamine neurons, the effects of pain on the reward pathway was completely reversed and the rats regained the motivation to push the lever and obtain their sugar tablet even with the sensation of pain.

In another round of lab experimentation, the team were able to reach the same effects by blocking the activity of neurons which produce GABA in response to pain. The rats who were part of this round of testing were similarly motivated to pick a solution of water and sugar over plain water even when experiencing pain. This, the authors explain, shows that the rats were better able to feel pleasure despite also experiencing pain.

All in all, even though the findings are valuable in and of themselves, the team says that this is the first time a link has been established between pain, an increase of activity of GABA neurons, and an inhibitory pathway effect in the reward system which causes decreased activity of dopamine neurons.

“Pain has primarily been studied at peripheral sites and not in the brain, with a goal of reducing or eliminating the sensory component of pain. Meanwhile, the emotional component of pain and associated comorbidities such as depression, anxiety, and lack of ability to feel pleasure that accompany pain has been largely ignored,” said study author Jose Morón-Concepcion, Ph.D., of Washington University in St. Louis.

“It is fulfilling to be able to show pain patients that their mental health and behavioral changes are as real as the physical sensations, and we may be able to treat these changes someday,” added study author Meaghan Creed, Ph.D., of Washington University in St. Louis.

The paper “Pain induces adaptations in ventral tegmental area dopamine neurons to drive anhedonia-like behavior” has been published in the journal Nature Neuroscience.

No Fun Allowed.

Researchers identify neurons that shut down rewards and motivation in the brains of mice

New research is pushing mice to their breaking point to see what our brain does as we give up.

No Fun Allowed.

Image credits Lagrevehumaine / Wikimedia.

A group of cells known as nociceptin neurons get busy when we’re giving up, new research shows. True to their name, these neurons release nociceptin, a complex molecule that suppresses dopamine. Dopamine is a neurotransmitter that underpins the brain’s pleasure and reward networks. The findings offer us a fresh take on the processes that govern motivation.

Giveupceptin

“We are taking an entirely new angle on an area of the brain known as VTA [ventral tegmental area],” said co-lead author Christian Pedersen, a fourth-year Ph.D. student in bioengineering at the University of Washington School of Medicine and the UW College of Engineering. “The big discovery is that large complex neurotransmitters known as neuropeptides have a very robust effect on animal behavior by acting on the VTA,” said Pedersen.

Nociceptin neurons are located near the VTA, a brain area that houses the hormones that release dopamine during pleasurable activities. This study took four years to complete and, according to the team, is the first one to describe the effects of the nociceptin modulatory system on dopamine neurons. The team hopes their findings will lead to new ways of helping people find motivation when they are depressed or decrease motivation for drug use in substance-abuse disorders.

The team worked with mice that they trained to seek out sucrose (sugar). To do this, the animals had to poke their snout into a port. The team set-up their experiment in such a way that this task was very simple and straight-forward at first: one poke, one reward. Over time, however, it would take exponentially more pokes (two, five, so on) to get the reward — and eventually, the animals just gave up. All the while, the team monitored the mice’s neural activity.

These recordings showed that the nociceptin neurons act as ‘demotivators’ or ‘frustration’ neurons and became most active when mice stopped seeking sucrose — suggesting they put the brakes on motivation.

“We might think of different scenarios where people aren’t motivated like depression and block these neurons and receptors to help them feel better,” says senior author Michael Bruchas, professor of anesthesiology and pain medicine and of pharmacology at the University of Washington School of Medicine.

“That’s what’s powerful about discovering these cells. Neuropsychiatric diseases that impact motivation could be improved.”

The team explains that these neurons exist as a kind of insurance policy for mammals living in the wild. The reward pathways in our brains work to make us mammals maintain homeostasis (i.e. our internal ‘optimal running conditions’). However, in the wild, animals need a safety switch to keep them from pursuing rewards too much, as the environment tends to have limited resources and this pursuit of reward could impact the animal’s survival by expending too much energy, for example. Persistence in seeking uncertain rewards can also be disadvantageous due to risky exposure to predators, the researchers noted.

The paper “A Paranigral VTA Nociceptin Circuit that Constrains Motivation for Reward” has been published in the journal Cell.

Good bad choice.

Dopamine is the key allowing our brains to change beliefs — short-term ones, at least

Researchers have captured the first images of a brain changing its beliefs.

Good bad choice.

Image credits Fathromi Ramdlon.

It’s not easy being a brain. Among a host of other very complex tasks, this lump of gray matter is also responsible for accurately representing the surrounding world. Keeping these beliefs as true to reality as possible is literally a matter of life and death. As such, brains come equipped with mechanisms that allow them to ‘update’ their beliefs.

That tidbit likely comes as a surprise to anyone who has ever seen a comment section, however. Experience has thought us that most people hate having their beliefs challenged, and will defend them with a fury. So, what exactly makes a brain change a set of beliefs it holds? Well, a team of UK researchers was also very curious to know, so they set about studying the brains of participants as they changed (simple) beliefs.

It’s dope(amine)

“We form beliefs about the world based on the information we get from our senses. When our sensory perceptions surprise us, it could mean that the world has changed and this might cause us to update our beliefs,” explains lead researcher Matthew Nour, from the University College London and Kings College London.

“For example, if we are told that it’s sunny outside, and then we hear raindrops, then we modify our belief.”

Previous research has suggested that the neurotransmitter dopamine is related to the process of updating representations — at least in rodent brains. However, there was no direct evidence that human brains work through the same process, especially since it was very difficult to reliably measure dopamine functions in living people.

For the study, the team used a fMRI (functional magnetic resonance imaging) machine to peer into the brains of people as they were changing short-term beliefs and later tied these readings to the participants’ dopamine functions.

Volunteers were asked to respond to a series of sounds and images — some of which were meant to surprise. These latter ones, the team’s hypothesis went, would cause the participants to change their beliefs about the task environment, since ‘a surprise’ is something the brain didn’t expect, i.e. didn’t conform to its current beliefs. They used the fMRI scanner to measure changes in brain activity while these beliefs were changing, and measured activity in the dopamine system using PET scans — Positron Emission Tomography, which uses a small amount of radioactive tracer to measure dopamine receptors in the brain.

“We found that two key brain areas of the dopamine system (the midbrain and striatum) appear to be more active when a person updates their beliefs about the world, and this activity is related to measures of dopamine function in these regions,” Nour explains.

This is the first study to establish a direct link between dopamine activity and the process of updating beliefs in humans; the neurotransmitter has previously been linked to learning and the brain’s reward pathway.

Such findings could have several implications, especially pertaining to drugs or medicine that have a powerful impact on dopamine levels in the brain. Cocaine and amphetamine use, for example, “increase[s] brain dopamine release and can cause significant changes in our perceptions and beliefs about the surrounding world,” the team explains.

The paper could also improve our understanding of the several psychiatric disorders have also been tied to abnormal dopamine function. For example, in the case of schizophrenia, abnormal dopamine activity might impair the brain’s ability to update beliefs from outside input, potentially contributing to symptoms such as delusion.

Still, the findings are far from conclusive right now. The team looked at the brain activity of people changing simple beliefs about the causes of their perceptions. However, it points the way for future research into how the brain supports the formation of more general beliefs.

The paper “Dopaminergic basis for signaling belief updates, but not surprise, and the link to paranoia” has been published in the journal Proceedings of the National Academy of Sciences.

Waving away mosquitoes teaches them to stop bothering prey

A female mosquito dining at a fancy… human?
Source: Pixabay/skeeze

Mosquitoes rely on smell to choose victims. In a new study published in Current Biology, mosquitoes learned to associate smells with vibrations mimicking human hand movements. After subsequent exposures to the same smell, the arthropods avoided the respective odor. This behavior suggests that the insects learned that certain scents were associated with a near-death experience.

The smell of fear

Mosquitoes, these tiny, annoying vampires, bother everyone from birds to humans. They are not just terribly vexing, but dangerous as well. Even though the word ‘mosquito’ comes from Spanish and means ‘little fly’, the insects are not innocent at all. Mosquitoes are considered the deadliest animals on Earth, causing 725,000 deaths per year, according to a 2014 World Health Organization survey. Malaria, a mosquito-borne infectious disease, killed 445,000 people in 2016, states WHO.

These alarming numbers are the main reason why scientists are now trying to come up with different methods to reduce mosquito bites.

Previously, researchers discovered that each mosquito species shows a proclivity towards a certain type of host animal, even towards distinct individuals within those species. Unfortunately, the exact mechanisms through which this insect chooses its prey are still unknown. For example, generalist mosquito Culex tarsalis primarily torments birds in the summer but feeds on both mammals and birds in the winter.

Researchers at the University of Washington conducted an experiment to see if mosquito preferences could be learned. The team, led by Jeffrey Riffell, employed mosquitoes, rats, chickens and a machine named the “vortexer”. Scientists first presented the insects with an animal smell — a rat, for example. Next, the vortexer was used to inflict small mechanical shocks on mosquitoes.

A mosquito in the “vortexer” machine, which simulates swats. (Image: Kiley Riffell)

The following step was to assess if the mosquitoes learned something. Two groups of mosquitoes took part in the study: a control group of untrained mosquitoes and a group of previously trained ones. Researchers discovered that trained mosquitoes did not attack the rats, as the untrained ones did. When scientists repeated the experiment — but this time with chickens — they observed that the Aedes aegypti mosquitoes encountered some difficulty acquiring avian odors. The reason might be that the Aedes aegypti mosquitoes predominantly suck human blood, so they would be inclined to learn mammal smells faster.

“Once mosquitoes learned odors in an aversive manner, those odors caused aversive responses on the same order as responses to DEET, which is one of the most effective mosquito repellents,” said Riffell in a statement. “Moreover, mosquitoes remember the trained odors for days.” he added.

Scientists wondered how the small mosquito brain could process such a large amount of information. One answer came to mind: dopamine, a neurotransmitter that is frequently used in learning processes (especially in remembering with the help of good or bad stimuli) by mammals and insects alike.

The team had one more thing to do: to prove their theory right. So, they genetically engineered mosquitoes that lacked dopamine receptors and glued them to a rack in order to monitor their neuron activity when introducing them to different odors. The researchers discovered that neurons were less likely to fire when presented various smells due to their inability to process dopamine.

A mosquito glued to a 3D-printed rack. (Image: Kiley Riffell)

“By understanding how mosquitoes are making decisions on whom to bite, and how learning influences those behaviors, we can better understand the genes and neuronal bases of the behaviors,” said Riffell. “This could lead to more effective tools for mosquito control.”

So, if a mosquito is troubling you, feel free to wiggle your hands at it. You might not kill it, but there is a good chance it will leave you alone.

Personal Space Violation.

Scientists poke at the root of our need for personal space — using fruit flies

Feeling like people are invading your personal space? It’s dopamine that does it, researchers report.

Personal Space Violation.

Image credits Jeff Hitchcock / Flickr.

We’ve all been there. You’re having a chat with somebody one minute, and the next they’re simply too close. You didn’t make a conscious decision about this, didn’t settle on a ‘too near’ line, but you just know it’s being overrun at that exact moment. So you back away, almost by instinct.

You’d think we have a pretty good idea of what’s working in the background of a concept as universal as ‘personal space’ — but not really. That’s why a team led by Anne F. Simon of Western University’s Department of Biology started studying the need for social space and how it can be disrupted. They report that dopamine, a neurotransmitter best known for its role in the reward pathway of the brain, is a key substance in mediating social space.

A-buzz with dopamine

The team worked with Drosophila melanogaster, the common fruit fly, as they come with certain very desirable traits: they develop really fast, lay a lot of eggs, and are dirt-cheap to feed and care for. They’ve seen a lot of use in scientific pursuits, and they’re the insects Gregor Mendel used to lay the foundation of genetics.

Using genetic and pharmacological manipulations, the team tailored the neurons in some of the flies to produce more or less dopamine than those in unaltered fleas.

Their results show that dopamine is a key component in “the response to others in a social group, specifically, social spacing,” and could change how much space the flies need from each other. The effect was “prominent only in the day-time, and its effect varies depending on tissue, sex and type of manipulation.” For example, too little dopamine made male flies seek greater distances from each other, while too much dopamine made them close ranks. In female flies, both too much or too little release of dopamine made them increase social distance.

“Each animal has a preferred social bubble, a preferred personal space,” said Anne Simon.

“If we can connect the dots with other animals including humans — because we all have similar neurotransmitters — we may gain new ways of understanding what’s happening in some disorders where personal space can sometimes be an issue.”

That discovery may, in turn, have implications for better understanding conditions related to dopamine imbalances, such as schizophrenia or the autism spectrum, for example.

Next, the team plans to expand on the findings from the other way around, and find our how social cues influence dopamine release, and to identify the circuitry that regulates it.

“Ultimately, this research could lead us to understand a little better why some people are averse to social contact. It might also help us understand why some people who clearly want to interact don’t interpret some social cues the same way others might,” said Simon.

The paper “Modulation of social space by dopamine in Drosophila melanogaster, but no effect on the avoidance of the Drosophila stress odorant” has bee published in the journal Biology Letters.

Scientists see thoughts – and addiction – forming in the brain

Scientists managed to visualize the very formation of thoughts and addiction.

In a mouse brain, cell-based detectors called CNiFERs change their fluorescence when neurons release dopamine. Photo credits: Slesinger & Kleinfeld labs

A hundred years ago, the brilliant Russian physiologist Ivan Pavlov carried out what would become one of the most iconic experiments in science. Basically, before feeding his dogs, he would ring a bell. In time, the dogs associated the ringing of the bell with food and would get excited when they heard the bell ringing. Through a repeated procedure, he conditioned dogs to salivate at the ringing of a bell.

Now, we get to see that very process occurring in the brain. Ultimately, this could allow us to better understand learning, as well as addiction.

In order to study a neural system, you need some kind of stimulation, and then you need to record the effects of this stimulation in space and time. This is not an easy feat, and the team had to create a new type of biosensors.

“We developed cell-based detectors called CNiFERs that can be implanted in a mouse brain and sense the release of specific neurotransmitters in real time,” says Paul A. Slesinger, Ph.D., who used this tool to revisit Pavlov’s experiment. Neurotransmitters are the chemicals that transmit messages from one neuron to another.

CNiFERs are “cell-based neurotransmitter fluorescent engineered reporters.” They are the first biosensor which can reliably detect between the nearly identical neurotransmitters dopamine and norepinephrine. While the neurotransmitters are almost identical, distinguishing between them is huge, because they are associated respectively with pleasure and alertness — two very different states.

They were also able to measure and image another interesting process: the dopamine surge. Like Pavlov’s dogs, Slesinger’s mice were excited when they knew they were receiving food.

“We were able to measure the timing of dopamine surges during the learning process,” Slesinger says. “That’s when we could see the dopamine signal was measured initially right after the reward. Then after days of training, we started to detect dopamine after the tone but before the reward was presented.”

This kind of dopamine surge is also associated with addiction, and the technology might one be used to assess someone’s addiction to something. Ultimately, Slesinger says they’d like to use this sensing technique to directly measure these neuromodulators, which affect the rate of neuron firing, in real time.

The research was presented at a meeting of the American Chemical Society and was not yet published in a peer-reviewed journal.

How dopamine is shuttled between neurons

University of Florida researchers have discovered how our bodies control dopamine transport in and out of brain cells. Their findings could be the starting point in developing more efficient treatments for drug addictions and several neurological disorders.

Dopamine is the ultimate feel-good substance. Known as the “pleasure molecule,” this amine underlies the brain’s motivation-reward pathway. When doing something you or your body thinks is important such as eating, having sex or getting a new high-score, dopamine gets released to motivate you to keep doing that activity. Basically, it’s the neurotransmitter equivalent of a high five.

But dopamine also acts as a neurotransmitter (chemicals that travel between neurons and relay infromation) in eight other brain structures, including the tongue-torturing nigrostriatal and tuberoinfundibular pathways.

I can barely type them without stuttering.
Image via learn.genetics.utah.edu

We’ll just call them the dopamine pathways. These structures have an important role to play in our brains and tampering with dopamine levels wreaks havoc on them. Too little can lead to Parkinson’s disease, a brain disorder that causes shaking and problems with movement and coordination. Abnormally high concentrations are linked to schizophrenia and other psychiatric disorders.

Knowing how a particular protein called dopamine transporter controls dopamine movement in and out of neurons is crucial to further understanding of these disorders, said Pharm D., Ph.D. Habibeh Khoshbouei, associate professor of neuroscience in the UF College of Medicine and co-author to the paper.

“It’s an important first step. If we know how the dopamine transport system works, then we can start fixing it when it’s broken or malfunctioning.”

The researchers used mouse and human-derived dopamine neurons to understand how dopamine travels through cell membranes. They found that this movement is controlled by changes in the neurons’ electrical properties (specifically, in the electrical potential on their membranes).

“Changes in the membrane potential alone, a universal yet dynamic cellular property, rapidly alter trafficking of DAT (dopamine active transporter proteins) to and from the surface membrane,” the paper’s abstract reads.

“Broadly, these findings suggest that cell-surface DAT levels are sensitive to membrane potential changes, which can rapidly drive DAT internalization from and insertion into the cell membrane, thus having an impact on the capacity for DAT to regulate extracellular dopamine levels.”

Khoshbuoei likenes the dopamine transporter to a powerful, efficient “vacuum cleaner” that maintains the brain’s chemical balance by rapidly absorbing dopamine back into the cells.

When the system works properly, dopamine is swept back into the neurons by the dopamine transporter, allowing the brain to return to a less-stimulated state. Substances such as cocaine or methamphetamine can keep the brain stimulated by preventing neurons from absorbing the excess dopamine.

A properly functioning dopamine system controls cognition, movement, reward and pleasurable feelings. Imbalance in the dopamine transport system leads to neurological and neuropsychiatric diseases. And understanding how the brain regulates its dopamine levels is the first step in helping those suffering from addiction or neurological disorders.

heavy_marijuana_use

Heavy marijuana users might damage their brain’s pleasure center

heavy_marijuana_use

Photo: http://mmfit1.wordpress.com/

While marijuana use is becoming less of a tabu, in light of medical legalization in places like Colorado, California or Uruguay, the same can’t be said about marijuana research. A while ago, I mentioned how only 6% of marijuana research studies the benefits, which is completely biased and absurd to begin with, considering policymakers have legalized the herb in many states. What’s troubling me is that we’re not talking about some new chemical or anything. We’re talking about a natural herb that’s been ingested for thousands of years and that’s currently being used by millions of people all over the world, yet we know very little about the potential beneficial or adverse effects to health. For instance, it might just be case that heavy marijuana use could rewire the way dopamine is being used in the brain’s pleasure center, leaving users feeling crummy and miserable. It might also be the case marijuana use could cure cancer, but we’re not seeing enough research done because scientists have too pass through four regulatory agencies, including the DEA, to study anything of the like.

(/rant) Back to heavy pot smokers and dopamine, researchers at the National Institute on Drug Abuse in Bethesda, Maryland wanted to see how the drug affects dopamine production and distribution in the brain. The neurotransmitter is triggered when undertaking pleasurable activities like eating, sex or taking some drugs. Some psychoactive substances, however, come with a big downer as a result of abuse. Alcoholics and cocaine addicts, for instance, are known to have serious trouble producing as much dopamine as non-users, which in turn makes them depressed and lifeless.

[ALSO READ] Addiction is a disease that first starts with dopamine overcorrection in the brain

Some studies have hinted that marijuana might also hijack the dopamine system, so Nora Volkow, the director of the National Institute on Drug Abuse in Bethesda, and her team decided to investigate further. The researchers gave methylphenidate, commonly known as Ritalin – a substance that increases the amount of dopamine found in the brain – to 24 marijuana abusers (who had smoked a median of about five joints a day, 5 days a week, for 10 years) and 24 controls.

Brain imaging showed that both controls and abusers produced roughly just as much extra dopamine, but what significantly differed was the witnessed effects. While the controls had higher heart rates, became more anxious and, basically, got high, the marijuana abusers didn’t report anything different happening with their bodies or mood – it just didn’t kick in for them!

[RELATED] Heavy marijuana use causes poor memory

This lack of response has prompted the researchers to believe the reward circuitry in the brains of heavy marijuana users might be damaged. Apparently, abusers and non-users produce just as much dopamine, but the way the neurotransmitter gets used differs which makes the whole situation really tricky. According to the people involved in the study, this disconnection might cause heavy marijuana smokers trouble finding pleasure in other-wise enjoyable, common activities. Ironically, heavy marijuana smokers might become stressed, irritable or depressed. And yet, it’s unclear from the study whether heavy marijuana users smoke a lot because they have a poor dopamine distribution network or their reward system is screwed because they smoke a lot. Not being able to tease out cause and effect “is a limitation in a study like this one,” Volkow says.

The report was published in the Proceedings of the National Academy of Sciences.

dopamine_drgs_pills-

Addiction is a disease that first starts with dopamine overcorrection in the brain

dopamine_drgs_pills-Drug and alcohol addiction affects millions of people around the world, but despite decades worth of research and billions of dollars, our understanding of addiction is still far from being complete. Brigham Young University professor Scott Steffensen and his team have recently contributed with a few pieces in the addiction puzzle, which are of vital importance. Their work suggests that addiction starts with the brain’s attempts to correct excessive dopamine levels triggered by drugs.

“Addiction is a brain disease that could be treated like any other disease,” Steffensen said. “I wouldn’t be as motivated to do this research, or as passionate about the work, if I didn’t think a cure was possible.”

When you abuse the brain, the brain abuses back and heavily cuts on dopamine generation, even when you’re sober and needed it the most

Out of Steffenson’s lab, three research papers came out that detail the brain mechanism when dealing with addiction. The papers are about: withdrawal (The Journal of Neuroscience),  nicotine and alcohol interaction in the brain (The Journal of Pharmacology and Experimental Therapeutics), and the effects of cocaine addiction on the brain’s reward circuitry (Addiction Biology). In all of these cases the common denominator is a magic chemical: dopamine.

Dopamine is an important brain chemical in drug abuse and addiction. Many drugs affect dopamine transmission directly by either blocking or stimulating its receptors. For example, antipsychotic drugs are dopamine antagonists, whereas bromocriptine, used to treat hyperprolactinaemia and Parkinson’s disease, is a dopamine agonist. Most cases of addiction stem from drug abuse, causing an increase in brain dopamine (DA) levels, which at it’s own hand causes increased activity in the brain reward pathway – the pleasure and high feeling.

When drugs and alcohol release unnaturally high levels of dopamine in the brain’s pleasure system, oxidative stress occurs in the brain. Steffenson and his team found that the brain responds by generating a protein called BDNF (brain derived neurotrophic factor). This correcting behavior causes a suppression of dopamine generation, but continues to do so even long after a person had come off the high. So, while the brain was faced with dopamine overload during the drug’s high, afterward it is faced with dopamine deprivation. This dopamine deprivation is what causes the pains, distress and anxiety of withdrawal.

“The body attempts to compensate for unnatural levels of dopamine, but a pathological process occurs,” Steffensen said. “We think it all centers around a subset of neurons that ordinarily put the brakes on dopamine release.”

“I am optimistic that in the near future medical science will be able to reverse the brain changes in dopamine transmission that occur with drug dependence and return an ‘addict’ to a relatively normal state,” Steffensen continued. “Then the addict will be in a better position to make rational decisions regarding their behavior and will be empowered to remain drug free.”

Possibility of erasing unwanted memories emerges

For the first time in history, scientists from the Florida campus of The Scripps Research Institute (TSRI) have been able to eliminate dangerous drug-associated memories in mice and rats without apparently affecting other memories.

Erasing memories

Credit: © JohnKwan / Fotolia

Credit: © JohnKwan / Fotolia

If you’ve ever seen The Eternal Sunshine of the Spotless Mind (truly a remarkable movie, which I highly recommend) – you probably have mixed feelings about this, and you know just what kind of dangerous possibilities erasing memories opens – but researchers working on this research had an entirely different idea in mind. They set out to help recovering addicts and individuals suffering from post-traumatic stress disorder (PTSD), for which recovering memories can be devastating.

The way in which the human brain makes seemingly random associations and makes connections is still a blurry area – but researchers are taking baby steps towards understanding how these memories and connections form.

“Our memories make us who we are, but some of these memories can make life very difficult,” said Courtney Miller, a TSRI assistant professor who led the research. “Not unlike in the movie Eternal Sunshine of the Spotless Mind, we’re looking for strategies to selectively eliminate evidence of past experiences related to drug abuse or a traumatic event. Our study shows we can do just that in mice — wipe out deeply engrained drug-related memories without harming other memories.”

How it works

Producing a memory is a complex phenomenon which includes alteration of the structure of nerve cells via changes in the dendritic spines – small protrusions from a neuron’s dendrite that typically receives input from a single synapse. Normally, these structures change through the generation of actin, the protein that makes up the infrastructure of all cells.

dendritic spine

In this new study, researchers have inhibited actin polymerization — the creation of large chainlike molecules by blocking the molecular motor which generates them (called myosin II) in the brains of mice and rats during the maintenance phase of methamphetamine-related memory formation.

Behavioral tests conducted afterwards showed the animals lost any memories related to metamphetamine; it’s still unclear why relatively powerful drug-related memories are so fragile, but it’s believed these groundbreaking discoveries are connected to the role of dopamine, a neurotransmitter involved in reward and pleasure centers in the brain which is known to modify dendritic spines – so this method could possibly only work on dopamine-related memories.

“We are focused on understanding what makes these memories different. The hope is that our strategies may be applicable to other harmful memories, such as those that perpetuate smoking or PTSD.”

Journal Reference: Erica J. Young, Massimiliano Aceti, Erica M. Griggs, Rita A. Fuchs, Zachary Zigmond, Gavin Rumbaugh, Courtney A. Miller. Selective, Retrieval-Independent Disruption of Methamphetamine-Associated Memory by Actin Depolymerization. Biological Psychiatry, 2013; DOI: 10.1016/j.biopsych.2013.07.036

Better Dressed Dopamine

My name is Victoria and I am a shopaholic. I mean it!

The feeling I will soon describe will be familiar to millions: a surge of excitement as they find that must-have item in the shop, followed by a sickening sense of let-down shortly afterwards.

It may be some relief to discover that scientists not only know why it happens and can now provide some pointers or theraphy to avoiding it.

The feeling is caused by the release of a specific chemical in the brain. A very special one! One ralated to cocaine, heroin and methamphetamine consumption among others. Dopamine, a chemical associated with pleasure, is released in waves as shoppers first see a product and then consider buying it.But the more recent news is that the anticipation rather than the buying itself produces the discharge of the chemical and drives the process. The effect of the naturally produced chemical lasts only a short time and can leave the shopper feeling let down when brain chemistry returns to normal. Rats release dopamine when they see a new part of the cage to explore, but the level drops quickily once they enter it.

“Dopamine is all about the hunt and the anticipation. It is released as you conjure up in your mind the thought of this purchase and anticipate how it will look and how you will use it.” Gregory Berns,  neuroscientist at Emory University

Neuroco, a London consulting firm, uses portable monitors strapped to shoppers to produce “brain maps”. These studies can be quite beneficial for retailers, who benefit greatly from understanding what keeps costumers entering the shop.

Dopamine is also related to survival, but nowadays it may be more about the urban jungle. If a woman sees a dress that can help her “survive” or increase her social status at some party, she will see it as a “must have”. But if she buys it, the euphoric feeling will soon be gone. On the other hand, a more profound feeling of dissapointment will set into  place if she does not buy it. Both ways, she will be even harder to satisfy the next time as she needs a “biger dose”.  So, what can she do?

First of all, try to first visit new shops after the closing hour or check out the collection on the web page. Entering a store you have seen before will not produce such a strong effect. Secondly, avoid shopping sprees in new areas or cities or simply leave the credit card at home. Going with friends will only make the feeling more intense.  Buying and returning the product is also a very bad idea.

Last, but not least….think of the enviromental impact of such bad and impulsive shopping!

Scientists give computers schizophrenia to better understand the human brain

Researchers from the University of Texas and Yale infected a computer with schizophrenia in order to find out more about how the human brain behaves and understands things.

Human behaviour from a computer

Computers can show some signs of virtual schizophrenia too, if they can’t ‘forget’ fast enough. So researchers used a virtual computer model, which is also called a ‘neural network’, to simulate the excessive release of dopamine in the brain. The dopamine hypothesis of schizophrenia is a model attributing symptoms of schizophrenia to an increased and unnatural level of dopamine production. They found that the network recalls memories in a distinctly schizophrenic-like fashion.

“The hypothesis is that dopamine encodes the importance-the salience-of experience,” says Uli Grasemann, a graduate student in the Department of Computer Science at The University of Texas at Austin. “When there’s too much dopamine, it leads to exaggerated salience, and the brain ends up learning from things that it shouldn’t be learning from.”

Too much is too much

The results they got sustain the idea that in some people who learn too many things, the brain can lose the ability to forget and ignore as much as it would normally do. Without forgetting to ignore what’s unimportant, the brain would also lack the ability to extract what’s important from the immensity of stimuli that it would receive. Basically, these people start getting lost in a sea of connections, and start making ones that aren’t real, as well as not understanding the ones that are.

This is one of the big theories regarding the development of schizophrenia, and the study could give some valuable directions in understanding, and eventually preventing and treating the disease.

A neural model

They model they used is called DISCERN. It was designed by Professor Risto Miikkulainen, and it is able to do a variety of things, including learning a real language. In this study, DISCERN was used to simulate what happens to language as the result of eight different types of neurological dysfunction. After this, the results were in the hand of Yale professor Ralph Hoffman, professor of psychiatry, who compared them with what he saw when studying schizophreniacs.

“With neural networks, you basically train them by showing them examples, over and over and over again,” says Grasemann. “Every time you show it an example, you say, if this is the input, then this should be your output, and if this is the input, then that should be your output. You do it again and again thousands of times, and every time it adjusts a little bit more towards doing what you want. In the end, if you do it enough, the network has learned.”

In order to modelate the hyperlearning that was needed for this schizophrenia study, they ran the system again and again, but with one key parameter altered. They also increased the system’s learn rate, essentially by telling it to forget so much, thus simulating the excessive release of dopamine.

“It’s an important mechanism to be able to ignore things,” says Grasemann. “What we found is that if you crank up the learning rate in DISCERN high enough, it produces language abnormalities that suggest schizophrenia.”

Questions are still open

The parallel between the computer model and humans isn’t perfect, so this still isn’t definitive proof that the hyperlearning schizophrenia model is correct. However, it does support the hypothesis, and with computer models becoming better and better, scientists can hope to rely on them more and more, especially because you can have much more control over neural networks than you can have on humans.

Alcohol helps the brain remember

The effects alcohol has on our brain are still not perfectly understood, and the general opinion and even some studies are biased because… well, generally speaking, alcohol is bad for you, and we tend to forget that students drink, teachers drink, scientists and artists drink. But according to a study conducted by the Waggoner Center for Alcohol and Addiction Research at The University of Texas at Austin, it may not be all bad: drinking alcohol causes certain areas of our brain to learn and remember better.

Well not quite... but the picture is just too funny

“Usually, when we talk about learning and memory, we’re talking about conscious memory,” says Morikawa, whose results were published last month in The Journal of Neuroscience. “Alcohol diminishes our ability to hold on to pieces of information like your colleague’s name, or the definition of a word, or where you parked your car this morning. But our subconscious is learning and remembering too, and alcohol may actually increase our capacity to learn, or ‘conditionability,’ at that level.”

Morikawa’s study found that repeated ethanol exposure enhances synapticgo plasticity in a key area in the brain, which basically helps you learn and remember some things better. When you drink alcohol (or take cocaine or heroine, for example), the subconscious is learning to take more and more, and it wants more and more, but it doesn’t stop there. We become more and more receptive to subconscious memories and habits with respect to food, music, even people and social situations.

If you take alcoholics, they aren’t addicted to the pleasure and relief they get with drinking alcohol; it’s the environmental, behavarioral and social changes they want so badly and which trigger dopamine release in the brain.

“People commonly think of dopamine as a happy transmitter, or a pleasure transmitter, but more accurately it’s a learning transmitter,” says Morikawa. “It strengthens those synapses that are active when dopamine is released.”

But hey, don’t go shouting off to your friends that alcohol is good for you; just tell them that… maybe it’s not necessarily as bad as everybody things.