serotonin receptors

Molecule of the Day - Serotonin

Serotonin (C10H12N2O), also known as 5-hydroxytryptamine (5-HT), is a white solid that is slightly soluble in water under standard conditions. Like dopamine (Day 44), it is an important neurotransmitter that regulates vital processes in the body.

In the brain, serotonin is largely produced in the neurons of raphe nuclei, which are found in the brain stem. It regulates perceptions of resource availability, which can affect bodily functions and sensations such as mood, appetite, digestion, and sleep.

Serotonin is released from the presynaptic neuron into the synaptic cleft via the fusing of serotonin-containing vesicles with the presynaptic membrane. It then binds to 5-HT receptors on the postsynaptic membrane. 

There are many different subtypes of 5-HT receptors, and each produces a different cellular response upon binding of serotonin. For example, the binding of serotonin to 5-HT2A receptors results in psychedelia, whereas the binding of serotonin to 5-HT3 receptors results in vomiting.

Due to the diverse functions of serotonin in different cells, many classes of drugs, such as anxiolytics, antidepressants, antiemetics, and antimigraine drugs, are designed to target the serotonin system. 

For example, selective serotonin reuptake inhibitors (SSRIs), such as sertraline (Zoloft) inhibit the reuptake of serotonin into the presynaptic membrane from the synaptic cleft. This increases the concentration of serotonin in the synaptic cleft, and the increased binding of serotonin to the 5-HT receptors. This results in an anxiolytic, antidepressive effect.

On the other hand, drugs such as ondansetron act on the receptors themselves; they act as antagonists to 5-HT3 receptors, preventing serotonin from binding to it. As a result, there is a reduction in nausea and vomiting, which are common side-effects in chemotherapy. Hence, such antiemetics are useful and are often co-administered together with chemotherapeutic agents.

In the human body, tryptophan is first hydroxylated via the action of tryptophan hydroxylase to produce 5-hydroxytryptophan, which is then decarboxylated by aromatic amino acid decarboxylase to produce serotonin.

Why LSD Makes You Feel “One With The Universe”

by Saṃsāran  

LSD users often associate their experiences under the drug with a sense of connectedness to things that had gone unnoticed before. This effect is the factor which makes people attach such a powerful feeling of unity and purpose to the experience but also why this feeling does not last. 

It is only a trick of the brain, not a mystical journey.

Recently a study was done and it was determined that a particular kind of receptor in the brain for serotonin called “5-HT2A” was responsible for this effect. A study was done where scientists played music for the test subjects. The students in the LSD group found deep meaning in most of the music while the control group did not. 

The study then tested this effect in patients who first received a drug that specifically blocks the 5-HT2A serotonin receptors in the brain while leaving other serotonin receptors affected by LSD untouched. In these people, the effect vanished. They didn’t discover meaning in the songs as when they weren’t under the effects of LSD. 

The 5-HT2A receptor, the researchers conclude, is responsible for modulating how we attach meaning to objects, people and concepts in or lives. A distorted ability to attribute meaning to experience is a common hallmark of some mental diseases, and establishing a defined pathway by which this happens could offer new routes for treatment.

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fictional characters + mbti 

Like a hard drive blasted by excessive voltage, my mind is frayed, close to fried. I can feel the static running through my brain. Serotonin receptors working overtime.

The INTP has a sharp ability to break down systems and people, and deconstruct them. Knowledge is their friend, as is logic. Offering a wide variety of theories, their enthusiasm is something that is remarkable as is also their willingness to take on intellectual challenges. 

It is not uncommon for an INTP to have a world of knowledge and facts that they can share. They may be shy, cynical and have problems relating to others. There is no denying the independence of an INTP to think outside of the box, be imaginative and have theories no one would even consider, and are trustworthy in implementing a logical alternative.

Forever thirsty for more information and stimulus for the mind, INTP’s ask the questions no one would dare to ask, and push the world to exciting, deep places.

Characters: Luna Lovegood, Samwell Tarly, Smaug, Suzanne Warren, Spencer Reid, Elliot Alderson

The effect of ecstasy on serotonin receptors in your brain. Ecstasy also known as MDMA completely damages serotonin receptors. 

Image courtesy of Dr. GC Ricaurte of Johns Hopkins University School of Medicine 

Don’t do drugs kids! 

Researchers Shed Light on How Neurons Exchange Neurotransmitters

For more than a century, neuroscientists have known that nerve cells talk to one another across the small gaps between them, a process known as synaptic transmission (synapses are the connections between neurons). Information is carried from one cell to the other by neurotransmitters such as glutamate, dopamine, and serotonin, which activate receptors on the receiving neuron to convey excitatory or inhibitory messages.

But beyond this basic outline, the details of how this crucial aspect of brain function occurs have remained elusive. Now, new research by scientists at the University of Maryland School of Medicine (UM SOM) has for the first time elucidated details about the architecture of this process. The paper was published in the journal Nature.

Synapses are very complicated molecular machines. They are also tiny: only a few millionths of an inch across. They have to be incredibly small, since we need a lot of them; the brain has around 100 trillion of them, and each is individually and precisely tuned to convey stronger or weaker signals between cells.

To visualize features on this sub-microscopic scale, the researchers turned to an innovative technology known as single-molecule imaging, which can locate and track the movement of individual protein molecules within the confines of a single synapse, even in living cells. Using this approach, the scientists identified an unexpected and precise pattern in the process of neurotransmission. The researchers looked at cultured rat synapses, which in terms of overall structure are very similar to human synapses.

(Image caption: Synapses visualized in live neurons. The overall structure of one cell in a dense network of interconnected neurons is visible from expression of a red and green fluorescent protein that fills that cell entirely)

“We are seeing things that have never been seen before. This is a totally new area of investigation,” said Thomas Blanpied, PhD, Associate Professor in the Department of Physiology, and leader of the group that performed the work. “For many years, we’ve had a list of the many types of molecules that are found at synapses, but that didn’t get us very far in understanding how these molecules fit together, or how the process really works structurally. Now by using single-molecule imaging to map where many of the key proteins are, we have finally been able to reveal the core architectural structure of the synapse.”

In the paper, Blanpied describes an unexpected aspect to this architecture that may explain why synapses are so efficient, but also susceptible to disruption during disease: at each synapse, key proteins are organized very precisely across the gap between cells. “The neurons do a better job than we ever imagined of positioning the release of neurotransmitter molecules near their receptors,” Blanpied says. “The proteins in the two different neurons are aligned with incredible precision, almost forming a column stretching between the two cells.” This proximity optimizes the power of the transmission, and also suggests new ways that this transmission can be modified.

Blanpied’s lab has created a video representation of the process.

Understanding this architecture will help clarify how communication within the brain works, or, in the case of psychiatric or neurological disease, how it fails to work. Blanpied is also focusing on the activity of “adhesion molecules,” which stretch from one cell to the other and may be important pieces of the “nano-column.” He suspects that if adhesion molecules are not placed correctly at the synapse, synapse architecture will be disrupted, and neurotransmitters won’t be able to do their jobs. Blanpied hypothesizes that in at least some disorders, the issue may be that even though the brain has the right amount of neurotransmitter, the synapses don’t transmit these molecules efficiently.

Blanpied says that this improved comprehension of synaptic architecture could lead to a better understanding of brain diseases such as depression, schizophrenia and Alzheimer’s disease, and perhaps suggest new ideas for treatments.

Blanpied and his colleagues will next explore whether the synaptic architecture changes in certain disorders: they will begin by looking at a synapses in a mouse model of the pathology in schizophrenia.

“The complexity of the human brain seems overwhelming. But Dr. Blanpied and his colleagues have taken an important step in helping us understand this system,” said UM SOM Dean E. Albert Reece MD, PhD, MBA, who is also vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor. “This study is impressive scientifically, and it is just the first step of what I am sure will be a long series of important discoveries about the brain and its disorders.”

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“Like a hard drive blasted by excessive voltage, my mind is frayed. Close to fried. I can feel the static running through my brain. Serotonin receptors working overtime.”

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