Tag Archives: brain

Drugs and the Brain

03 Thursday Dec 2020

Posted by in brain, drugs, research, Uncategorized

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The human brain is the most complex organ in the body. This three-pound mass of gray and white matter sits at the center of all human activity—you need it to drive a car, to enjoy a meal, to breathe, to create an artistic masterpiece, and to enjoy everyday activities. In brief, the brain regulates your body’s basic functions; enables you to interpret and respond to everything you experience; and shapes your thoughts, emotions, and behavior.

The brain is made up of many parts that all work together as a team. Different parts of the brain are responsible for coordinating and performing specific functions. Drugs can alter important brain areas that are necessary for life-sustaining functions and can drive the compulsive drug abuse that marks addiction. Brain areas affected by drug abuse include: 

  • The brain stem, which controls basic functions critical to life, such as heart rate, breathing, and sleeping.
  • The cerebral cortex, which is divided into areas that control specific functions. Different areas process information from our senses, enabling us to see, feel, hear, and taste. The front part of the cortex, the frontal cortex or forebrain, is the thinking center of the brain; it powers our ability to think, plan, solve problems, and make decisions.
  • The limbic system, which contains the brain’s reward circuit. It links together a number of brain structures that control and regulate our ability to feel pleasure. Feeling pleasure motivates us to repeat behaviors that are critical to our existence. The limbic system is activated by healthy, life-sustaining activities such as eating and socializing—but it is also activated by drugs of abuse. In addition, the limbic system is responsible for our perception of other emotions, both positive and negative, which explains the mood-altering properties of many drugs.

How do the parts of the brain communicate?

The brain is a communications center consisting of billions of neurons, or nerve cells. Networks of neurons pass messages back and forth among different structures within the brain, the spinal cord, and nerves in the rest of the body (the peripheral nervous system). These nerve networks coordinate and regulate everything we feel, think, and do.

  • Neuron to Neuron
    Each nerve cell in the brain sends and receives messages in the form of electrical and chemical signals. Once a cell receives and processes a message, it sends it on to other neurons.
  • Neurotransmitters – The Brain’s Chemical Messengers
    The messages are typically carried between neurons by chemicals called neurotransmitters.
  • Receptors – The Brain’s Chemical Receivers
    The neurotransmitter attaches to a specialized site on the receiving neuron called a receptor. A neurotransmitter and its receptor operate like a “key and lock,” an exquisitely specific mechanism that ensures that each receptor will forward the appropriate message only after interacting with the right kind of neurotransmitter.
  • Transporters – The Brain’s Chemical Recyclers
    Located on the neuron that releases the neurotransmitter, transporters recycle these neurotransmitters (that is, bring them back into the neuron that released them), thereby shutting off the signal between neurons. soa_013.gif

To send a message, a brain cell (neuron) releases a chemical (neurotransmitter) into the space (synapse) between it and the next cell. The neurotransmitter crosses the synapse and attaches to proteins (receptors) on the receiving brain cell. This causes changes in the receiving cell—the message is delivered.

How do drugs work in the brain?

Drugs are chemicals that affect the brain by tapping into its communication system and interfering with the way neurons normally send, receive, and process information. Some drugs, such as marijuana and heroin, can activate neurons because their chemical structure mimics that of a natural neurotransmitter. This similarity in structure “fools” receptors and allows the drugs to attach onto and activate the neurons. Although these drugs mimic the brain’s own chemicals, they don’t activate neurons in the same way as a natural neurotransmitter, and they lead to abnormal messages being transmitted through the network.

Other drugs, such as amphetamine or cocaine, can cause the neurons to release abnormally large amounts of natural neurotransmitters or prevent the normal recycling of these brain chemicals. This disruption produces a greatly amplified message, ultimately disrupting communication channels.

How do drugs work in the brain to produce pleasure?

Most drugs of abuse directly or indirectly target the brain’s reward system by flooding the circuit with dopamine. Dopamine is a neurotransmitter present in regions of the brain that regulate movement, emotion, motivation, and feelings of pleasure. When activated at normal levels, this system rewards our natural behaviors. Overstimulating the system with drugs, however, produces euphoric effects, which strongly reinforce the behavior of drug use—teaching the user to repeat it.

Most drugs of abuse target the brain’s reward system by flooding it with dopamine.

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How does stimulation of the brain’s pleasure circuit teach us to keep taking drugs?

Our brains are wired to ensure that we will repeat life-sustaining activities by associating those activities with pleasure or reward. Whenever this reward circuit is activated, the brain notes that something important is happening that needs to be remembered, and teaches us to do it again and again without thinking about it. Because drugs of abuse stimulate the same circuit, we learn to abuse drugs in the same way.

Why are drugs more addictive than natural rewards?

When some drugs of abuse are taken, they can release 2 to 10 times the amount of dopamine that natural rewards such as eating and sex do.15 In some cases, this occurs almost immediately (as when drugs are smoked or injected), and the effects can last much longer than those produced by natural rewards. The resulting effects on the brain’s pleasure circuit dwarf those produced by naturally rewarding behaviors.16,17The effect of such a powerful reward strongly motivates people to take drugs again and again. This is why scientists sometimes say that drug abuse is something we learn to do very, very well.

Long-term drug abuse impairs brain functioning.

What happens to your brain if you keep taking drugs?

For the brain, the difference between normal rewards and drug rewards can be described as the difference between someone whispering into your ear and someone shouting into a microphone. Just as we turn down the volume on a radio that is too loud, the brain adjusts to the overwhelming surges in dopamine (and other neurotransmitters) by producing less dopamine or by reducing the number of receptors that can receive signals. As a result, dopamine’s impact on the reward circuit of the brain of someone who abuses drugs can become abnormally low, and that person’s ability to experience anypleasure is reduced.

This is why a person who abuses drugs eventually feels flat, lifeless, and depressed, and is unable to enjoy things that were previously pleasurable. Now, the person needs to keep taking drugs again and again just to try and bring his or her dopamine function back up to normal—which only makes the problem worse, like a vicious cycle. Also, the person will often need to take larger amounts of the drug to produce the familiar dopamine high—an effect known as tolerance.

Decreased Dopamine Transporters in a Methamphetamine Abuser18

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How does long-term drug taking affect brain circuits?

We know that the same sort of mechanisms involved in the development of tolerance can eventually lead to profound changes in neurons and brain circuits, with the potential to severely compromise the long-term health of the brain. For example, glutamate is another neurotransmitter that influences the reward circuit and the ability to learn. When the optimal concentration of glutamate is altered by drug abuse, the brain attempts to compensate for this change, which can cause impairment in cognitive function. Similarly, long-term drug abuse can trigger adaptations in habit or non-conscious memory systems. Conditioning is one example of this type of learning, in which cues in a person’s daily routine or environment become associated with the drug experience and can trigger uncontrollable cravings whenever the person is exposed to these cues, even if the drug itself is not available. This learned “reflex” is extremely durable and can affect a person who once used drugs even after many years of abstinence.

What other brain changes occur with abuse?

Chronic exposure to drugs of abuse disrupts the way critical brain structures interact to control and inhibit behaviors related to drug use. Just as continued abuse may lead to tolerance or the need for higher drug dosages to produce an effect, it may also lead to addiction, which can drive a user to seek out and take drugs compulsively. Drug addiction erodes a person’s self-control and ability to make sound decisions, while producing intense impulses to take drugs.

Serotonin deficiency may not be linked to depression

19 Friday Jul 2019

Posted by in brain, Depression, mental health, Neuroscience, Uncategorized

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Depression strikes some 35 million people worldwide, according to the World Health Organization, contributing to lowered quality of life as well as an increased risk of heart disease and suicide. Treatments typically include psychotherapy, support groups and education as well as psychiatric medications. SSRIs, or selective serotonin reuptake inhibitors, currently are the most commonly prescribed category of antidepressant drugs in the U.S., and have become a household name in treating depression.feelings-54.jpg

The action of these compounds is fairly familiar. SSRIs increase available levels of serotonin, sometimes referred to as the feel-good neurotransmitter, in our brains. Neurons communicate via neurotransmitters, chemicals which pass from one nerve cell to another. A transporter molecule recycles unused transmitter and carries it back to the pre-synaptic cell. For serotonin, that shuttle is called SERT (short for “serotonin transporter”). An SSRI binds to SERT and blocks its activity, allowing more serotonin to remain in the spaces between neurons. Yet, exactly how this biochemistry then works against depression remains a scientific mystery.

In fact, SSRIs fail to work for mild cases of depression, suggesting that regulating serotonin might be an indirect treatment only. “There’s really no evidence that depression is a serotonin-deficiency syndrome,” says Alan Gelenberg, a depression and psychiatric researcher at The Pennsylvania State University. “It’s like saying that a headache is an aspirin-deficiency syndrome.” SSRIs work insofar as they reduce the symptoms of depression, but “they’re pretty nonspecific,” he adds.

Now, research headed up by neuroscientists David Gurwitz and Noam Shomron of Tel Aviv University in Israel supports recent thinking that rather than a shortage of serotonin, a lack of synaptogenesis (the growth of new synapses, or nerve contacts) and neurogenesis (the generation and migration of new neurons) could cause depression. In this model lower serotonin levels would merely result when cells stopped making new connections among neurons or the brain stopped making new neurons. So, directly treating the cause of this diminished neuronal activity could prove to be a more effective therapy for depression than simply relying on drugs to increase serotonin levels.

Evidence for this line of thought came when their team found that cells in culture exposed to a 21-day course of the common SSRI paroxetine (Paxil is one of the brand names) expressed significantly more of the gene for an integrin protein called ITGB3 (integrin beta-3). Integrins are known to play a role in cell adhesion and connectivity and therefore are essential for synaptogenesis. The scientists think SSRIs might promote synaptogenesis and neurogenesis by turning on genes that make ITGB3 as well as other proteins that are involved in these processes. A microarray, which can house an entire genome on one laboratory slide, was used to pinpoint the involved genes. Of the 14 genes that showed increased activity in the paroxetine-treated cells, the gene that expresses ITGB3 showed the greatest increase in activity. That gene,ITGB3, is also crucial for the activity of SERT. Intriguingly, none of the 14 genes are related to serotonin signaling or metabolism, and, ITGB3 has never before been implicated in depression or an SSRI mode of action.

These results, published October 15 2013 in Translational Psychiatry, suggest that SSRIs do indeed work by blocking SERT. But, the bigger picture lies in the fact that in order to make up for the lull in SERT, more ITGB3 is produced, which then goes to work in bolstering synaptogenesis and neurogenesis, the true culprits behind depression. “There are many studies proposing that antidepressants act by promoting synaptogenesis and neurogenesis,” Gurwitz says. “Our work takes one big step on the road for validating such suggestions.”

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The research is weakened by its reliance on observations of cells in culture rather than in actual patients. The SSRI dose typically delivered to a patient’s brain is actually a fraction of what is swallowed in a pill. “Obvious next steps are showing that what we found here is indeed viewed in patients as well,” Shomron says.

The study turned up additional drug targets for treating depression—two microRNA molecules, miR-221 and miR-222. Essentially, microRNAs are small molecules that can turn a gene off by binding to it. The microarray results showed a significant decrease in the expression of miR-221 and miR-222, both of which are predicted to target ITGB3, when cells were exposed to paroxetine. So, a drug that could prevent those molecules from inhibiting the production of the ITGB3 protein would arguably enable the growth of more new neurons and synapses. And, if the neurogenesis and synaptogenesis hypothesis holds, a drug that specifically targeted miR-221 or miR-222 could bring sunnier days to those suffering from depression.

Exercise reorganizes the brain to be more resilient to stress

19 Wednesday Jun 2019

Posted by in brain, Exercise, mental health, research

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Physical activity reorganizes the brain so that its response to stress is reduced and anxiety is less likely to interfere with normal brain function, according to a research team based at Princeton University.

 

The researchers report in the Journal of Neuroscience that when mice allowed to exercise regularly experienced a stressor — exposure to cold water — their brains exhibited a spike in the activity of neurons that shut off excitement in the ventral hippocampus, a brain region shown to regulate anxiety.

These findings potentially resolve a discrepancy in research related to the effect of exercise on the brain — namely that exercise reduces anxiety while also promoting the growth of new neurons in the ventral hippocampus. Because these young neurons are typically more excitable than their more mature counterparts, exercise should result in more anxiety, not less. The Princeton-led researchers, however, found that exercise also strengthens the mechanisms that prevent these brain cells from firing.

 

The Brain and Emotional Self-Control

19 Tuesday Feb 2019

Posted by in brain, emotions, Self Esteem, Self-Care

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Different brain areas are activated when we choose to suppress an emotion, compared to when we are instructed to inhibit an emotion, according a new study from the UCL Institute of Cognitive Neuroscience and Ghent University.

In this study, published in Brain Structure and Function, the researchers scanned the brains of healthy participants and found that key brain systems were activated when choosing for oneself to suppress an emotion. They had previously linked this brain area to deciding to inhibit movement.feelings-51

“This result shows that emotional self-control involves a quite different brain system from simply being told how to respond emotionally,” said lead author Dr Simone Kuhn (Ghent University).

In most previous studies, participants were instructed to feel or inhibit an emotional response. However, in everyday life we are rarely told to suppress our emotions, and usually have to decide ourselves whether to feel or control our emotions.

In this new study the researchers showed fifteen healthy women unpleasant or frightening pictures. The participants were given a choice to feel the emotion elicited by the image, or alternatively to inhibit the emotion, by distancing themselves through an act of self-control.

The researchers used functional magnetic resonance imaging (fMRI) to scan the brains of the participants. They compared this brain activity to another experiment where the participants were instructed to feel or inhibit their emotions, rather than choose for themselves.

Different parts of the brain were activated in the two situations. When participants decided for themselves to inhibit negative emotions, the scientists found activation in the dorso-medial prefrontal area of the brain. They had previously linked this brain area to deciding to inhibit movement.

In contrast, when participants were instructed by the experimenter to inhibit the emotion, a second, more lateral area was activated.

“We think controlling one’s emotions and controlling one’s behaviour involve overlapping mechanisms,” said Dr Kuhn.

“We should distinguish between voluntary and instructed control of emotions, in the same way as we can distinguish between making up our own mind about what do, versus following instructions.”

Regulating emotions is part of our daily life, and is important for our mental health. For example, many people have to conquer fear of speaking in public, while some professionals such as health-care workers and firemen have to maintain an emotional distance from unpleasant or distressing scenes that occur in their jobs.

Professor Patrick Haggard (UCL Institute of Cognitive Neuroscience) co-author of the paper said the brain mechanism identified in this study could be a potential target for therapies.

“The ability to manage one’s own emotions is affected in many mental health conditions, so identifying this mechanism opens interesting possibilities for future research.

“Most studies of emotion processing in the brain simply assume that people passively receive emotional stimuli, and automatically feel the corresponding emotion. In contrast, the area we have identified may contribute to some individuals’ ability to rise above particular emotional situations.

“This kind of self-control mechanism may have positive aspects, for example making people less vulnerable to excessive emotion. But altered function of this brain area could also potentially lead to difficulties in responding appropriately to emotional situations.”