Dopamine addiction and drug usage

This week during the lecture a subject which was touched on was dopamine paths and receptors in the brain. Since dopamine creates pleasurable feelings when released, it can be easy to be addicted to any activity which releases the substance. One of the ways to release it is to use drugs, however many drugs cause significant negative health effects and death to the user if taken in too high concentrations which is easy to do due to their addictive nature.

When the neurotransmitter dopamine is released in the nucleus accumbens, the human mind feels the sensation of pleasure, hence the region is often referred to as the brain’s pleasure center. The intensity of pleasure depends on the amount of dopamine released in a short time period. Hence not all substances cause the same amount of pleasure, nor are they as addictive. As the mind is rewarded with a big dose of dopamine, it will be programmed to crave that same release. The intention of pleasure after all, is to motivate our mind to perform some beneficial action to either ourselves or to keep our species going. Hence eating tasty food and having sex release dopamine and are addicting.

brain slices

Drugs bypass the dose which is naturally possible to release, the amount can be up to 10 times higher compared to the previously mentioned methods. As the “intended” amount is exceeded, there are negative consequences. The problem with drug use is that the brain adapts to the overwhelming amount of dopamine which is released by producing much less dopamine and eliminating dopamine receptors to try to lower the quantity to normal levels. This causes the situation where more drugs need to be taken to achieve the same intensity of pleasure, and as less and less dopamine is available, ultimately the original level of pleasure becomes impossible. Thus, the doses of drugs taken become higher and the effects lower, and the brain increasingly craves the pleasurable feeling which it has been trained to expect.

Recreational drugs are not deadly in small doses, but as explained before the users are compelled to increase the dosage. Not all drugs are as deadly, but some of the more dangerous ones are opioids. Heroin for example, which is an opioid, kills by respiratory failure. Another example is Cocaine which kills by heart attack, and many prescription drugs can be overdosed.

Drug overdose is the leading cause of death for Americans under 50.

Posted by Markus Tayar

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Serotonin and depression

Currently, the lectures of the course are very much concentrated on neurotransmitters. I will use this as an excuse to write about depression and it’s medication.

As everything in neuroscience, depression can be seen from many different perspectives, and combining these gives us a wider field of vision. The perspectives I can offer are the neuroscientific one (based mainly on combination of Bear, Connors & Paradiso and Wikipedia) and the one of personal experience. I was diagnosed with depression last winter. Other useful point of view would be for example that of mental health care professionals’.

In colloquial language, depression has become a synonym of sadness. It is, however, more than that: a serious mental illness. Sadness and low mood are definitely symptoms of depression, but additionally there is for example lack of energy and motivation, a feeling of simple (and even fun and desirable) tasks being impossible to face. Additionally, sadness as a symptom of depression is different than as a regular feeling: it is generally more intense and doesn’t require a direct reason, instead being more like a positive feedback loop of negative emotions. On the other hand, depressed people aren’t necessarily always sad, and one can’t just decide someone is not depressed by just looking at their face.

Psychologically, depression might be triggered by stress or traumatic events, but typically this happens to people who have some kind of (genetic) susceptibility for it. From neurochemical perspective, this seems to be related to the neurotransmitter serotonin. Among other functions, this amine regulates mood.

Selective serotonin reuptake inhibitors, or SSRIs  for short, are one class of antidepressants. There are also other kinds of drugs against depression, but I will discuss only SSRIs here, because they are perhaps the most common kind and I have personal experience on them.

As the name suggests, SSRIs inhibit reuptake of serotonin to cells, increasing its concentration in synaptic cleft. Thus, the first interpretation would be, that SSRIs help the travel of of serotonin-mediated signals that are associated with positive feelings. The truth, however, is not as simple as that.  The anti-depression effects of these drugs take several weeks to really start showing. At that point, the cells have adapted to their presence by reducing the amount of serotonin receptors. It is not clear why this reduces the symptoms. One effect demonstrated is increased neurogenesis in hippocampus.

In addition to the science really not being settled, there is the fact that each individual human is different. There are many different kinds off SSRI drugs. Some of them work for some people and not for others. Some people will experience side effects. Scientific research can usually give us only general ideas. For example, some studies suggest that at least some SSRIs work better for people with more severe depression. For an individual, the only way to see if some specific (clinically approved) drug is suitable is trying it for couple of weeks, seeing how it feels and then possibly adjusting the dosage before waiting again for the effects to take place.

For example, I was first prescribed escitalopram. I felt that it made me more socially initiative, but the symptoms of depression kept getting worse. (At that point I didn’t have the depression diagnosis yet. The initial prescription was for anxiety, for which the SSRI medication is also used.) After I was barely able to handle my studies and other aspects of life even with highest dosage of escittalopram generally in use, I was switched to sertralin. Initial dose for that was also too small, but after a couple of times of adjusting it, the effects became clear. I have energy to study and do things I love. I have a working sleep cycle. I have lots of creative ideas. I feel like I have got my own personality and self back.

The medication isn’t a simple magical cure for depression. SSRIs have their problems. The important thing is that they can give the strength needed for rising from the depression. I have a weekly session with my psychotherapist and do mindfulness exercises to get better understanding and control over my emotions.

From our course book I learned that serotonin is made by cells from tryptophan, which we can get from many kinds of foods, including chocolate. It’s not scientifically proven that more dietary (non-purified) tryptophan leads to more serotonin in the brain, but chocolate can improve the mood in many ways 😉

So, remember to eat chocolate every now and then and please be kind to people with mental illnesses!

Posted by Mikko Luukinen

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Modeling neurotransmitter receptors

The third lecture and Chapter 5 of the course book handled synaptic transmission – especially chemical synapses, which play a huge role in developing effective psychoactive drugs, which could help e.g. in the treatment of depression and anxiety disorders. Chemical synapses work much more slowly than electric synapses, as it takes time for the release and diffusion of the neurotransmitter before the next neuron will be activated. The mechanisms of recycling the neurotransmitters are quite complex: in addition to simple diffusion, there are reuptake mechanisms which result in enzymatic degradation or recycling of the neurotransmitter. Alternatively, the transmitter can be degraded in the synaptic cleft. Autoreceptors at the presynaptic terminal often ensure that the signal transmission stops at some point.

As we have seen, the mechanisms and molecules related to synapses can be quite complex. It leaves you to wonder, how you could model the situation somewhat realistically. It must be essential to be able to, say, determine the proper dosage of psychoactive drugs. It should be understood, what the desirable levels of, for example, the monoamine neurotransmitters serotonin, dopamine or norepinephrine are. Excess and deficit amounts of these transmitters have been associated with many disorders, such as depression, ADHD and even schizophrenia [1].

One challenge is the discovery and analysis of the receptor structures involved in chemical synapses. Once it is known that by inhibiting a receptor we can have a certain effect on the brain, we have new questions. What kind of a molecule can we use to inhibit this receptor? What is the obtained level of inhibition? Modeling can offer some insight to this question. A pharmacophore is such a combination of features that defines how ligands are able to bind to a receptor. It may, for example, define locations of cationic and anionic groups and hydrophobic and hydrophilic parts of the molecule. The development of pharmacophore models and visual screening (VS) based on them can thus suggest molecules that would inhibit the receptor [2]. Drug development is often centered around the concept of trying to create compounds that have very similar structures to the ones that are known to work. Visual screening, however, can provide good potential inhibitors that have very different structures.

After this stage, however, many questions remain. How effective is that molecule in reality? Is it selective? Does it have potential side effects? Is it able to cross through the blood-brain-barrier? The deeper you go into this topic, the better you understand that we barely understand anything at all!

Posted by Meo Ekroos

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Brain Evolution

The 2nd week had us building a model of a brain using play dough in our first exercise session. This is to help us memorize the rough structure and parts that make up a human brain. Each person created their own brain with varying degrees of success.

A subject that also came up was the evolutionary history of the brain. The lower part of the brain, the reptilian brain, is the oldest part of the three sections of the brain. It controls heart rate, breathing, body temperature and balancing among other things. As the name suggests, a similar structure is found in the brain of reptiles.

Mammals have a limbic brain section, which records memories for behavior which creates disagreeable and agreeable experiences or human emotions. Emotions of course also effect our conscious or unconscious judgment. The limbic system is located in the middle of the brain.

And finally in primates or humans you have the neocortex. This section of the brain houses the functions that makes us human, language, abstract thought, imagination, philosophy, consciousness and so forth. The learning capabilities of the brain and all that that entails are also found here, and it is by far the biggest area in human brains.

parts

Posted by Markus Tayar

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The Interdisciplinary World of Neuroscience

Welcome to the Brain Fog, a learning diary blog for the course Structure and Operation of Human Brain at Aalto University. This week we had our first lecture. Most of the lecture was about practicalities, introductions and technical problems, so we didn’t get very deep in the subject itself.

However, we were for example introduced to the different spatial and temporal scales of neuroscience, from single action potentials to entire brains and even human societies they form. There was also discussion about consciousness, mainly how the word has multiple meanings thus doesn’t have an exact definition.

The main message of the lecture was, perhaps, that the brain is a physical system, that can be studied with natural sciences. It was also evident, that this research can be made from many different perspectives and backgrounds. One of the lecturers is a physicist, the another one a psychologist. The students of the course come from many different fields too. The brain is a vast and complex topic and requires interdisciplinary approach.

As the first lecture, so will this first blog post be about introductions. Here are the three students behind this learning diary:

Mikko Luukinen, BSc, has a background in engineering physics and is now beginning his neuroscience studies. His driving motivation is a dream of becoming a cyborg and revolutionizing humanity. Mikko has also worked on the BREAKBEN project.

Meo Ekroos is finishing his Bachelor’s degree in bioinformation technology and now starting his Master’s program in Biosystems and Biomaterials Engineering. He is in the field of technology out of both interest towards the world and passion for helping people. The question is, will he be of most help in the lab, beside a computer, or somewhere else, perhaps? Right now, he is a part of Finland’s team in the synthetic biology competition, iGEM.

Markus Tayar has studied physics for his Bachelor’s in Aalto University. He finds the idea of consciousness and how to influence it fascinating so he intends to major in Human Neuroscience and -technology. Another interest of his is nanotechnology, and some day he wishes to combine these topics to one in his line of work.

 

Posted by Mikko Luukinen

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