Serotonin and sleep

[libc.so.5]

Apologies if this is in the wrong place or if it has been discussed before, but I haven't been able to find a lot of information on this apart from on new-age and fitness websites.

As I understand it, stimulants mostly work on norepinephrine, dopamine and serotonin, increasing their levels of availability by either stimulating their release (e.g. MDMA, amphetamine etc.) or by inhibiting their re-uptake (e.g. methylphenidate, MDPV etc.).

Dopamine and norepinephrine, we hear, are responsible for the "get up and go" energetic feelings, and serotonin is associated with empathy and warmth - the MDMA "mid-week blues" are attributed to serotonin depletion.

But what part, exactly, does serotonin play in our sleep cycle?

In addition to being used to help soften the come-down from MDMA, metabolic precursors to serotonin such as L-tryptophan and 5-HTP are fairly commonly taken to help with insomnia. Users of MDAI, a selective serotonin releasing agent, report a sedated feeling.
This suggests, perhaps counter-intuitively, that an increase in serotonin levels should induce sleep.

However, Antidepressants and sleep : A qualitative review of the literature (which I could only find the abstract for) reports that SSRIs (such as fluoxetine/prozac) inhibit REM sleep. Some people in the MDAI thread report that although it made them feel relaxed and sleepy, they were not able to sleep.

Equivalent effects of acute tryptophan depletion on REM sleep in ecstasy users and controls agrees with the other study (showing that serotonin depletion allows for more REM sleep), but doesn't seem to show any significant difference in the total amount of sleep, does it? The results are on the page 6.

So what's going on? I would have thought that an increase in the levels of any of the "big three" neurotransmitters would wake you up rather than sending you to sleep, but some of these results seem to contradict that.
I suppose that it kind of makes sense, given that serotonin is classed together with melatonin as a tryptamine, whereas DA and NE are catecholamines.

I'd appreciate any information on the subject, thanks!

 

[KAYLA2010]

Look into the other neurotransmitter acetylcholine......everyone seems to forget that one.....anyways it controls a whole lot and it does effect REM......

 

[P A]

new-age and fitness websites.

Hmmm...I think I know where this is going.

As I understand it, stimulants mostly work on norepinephrine, dopamine and serotonin, increasing their levels of availability by either stimulating their release (e.g. MDMA, amphetamine etc.) or by inhibiting their re-uptake (e.g. methylphenidate, MDPV etc.).

Yup.

But what part, exactly, does serotonin play in our sleep cycle?

A pretty big and pretty complex one. Check out the "Forcing REM" thread and read the articles I posted for a small sample.

This suggests, perhaps counter-intuitively, that an increase in serotonin levels should induce sleep.

No. Quite a few drugs are notorious for causing concomitant sedation and insomnia, the neuroleptics standing out as apt poster-children for all nasty pychotropic drugs.

Dopamine and norepinephrine, we hear, are responsible for the "get up and go" energetic feelings, and serotonin is associated with empathy and warmth

Well then we hear wrong. Serotonin, or 5-Hydroxytryptamine, along with its respective family of functionally diverse receptors (5HT1-5HT7), is associated primarily with sensory perception, regulation of arousal, certain aspects of cognition/memory, mood, and hormonal regulation, among a few other essential biological functions. Simply increasing extracellular levels of this hormone alone typically causes [if anything at all] any of: anxiety, dizziness, gastric effects (diarrhea/constipation), hypertension, mild sedation, alternate cognitive impairment or enhancement, and sexual dysfunction. And by the way, I have to ask - why do all drug users with access Google nowadays consider themselves amateur neuroscientists?

Just so you know, so-called 'monoamine reductionism' is nothing more than a tired media ploy invented for the sole purpose of dishonestly persuading hapless consumers by appealing to their ignorance and gullibility. Depression is NOT a serotonin deficiency. Feeling tired is NOT symptomatic of "low dopamine levels," whatever the fuck that's even supposed to mean. And selective noradrenaline reuptake inhibitors don't wake you up. Shocking? The brain is a multifarious, highly complex facet of study, and referring to serotonin as being "associated with empathy and warmth" does nothing to further others' understanding (and in many cases likely hinders it). Just type 'serotonin' and 'sleep' into Pubmed for christ's sake.

And yeah, I know, you didn't actually mention any of the above fallacies, but you might as well have. Sorry the New Age websites got to you before skepticism and scientific inquiry...

 

[libc.so.5]

Look into the other neurotransmitter acetylcholine......everyone seems to forget that one.....anyways it controls a whole lot and it does effect REM......

Thanks, I will definitely look into this.

A pretty big and pretty complex one. Check out the "Forcing REM" thread and read the articles I posted for a small sample.

Quite a few drugs are notorious for causing concomitant sedation and insomnia, the neuroleptics standing out as apt poster-children for all nasty pychotropic drugs.

Again, thanks, I'll do some more reading on these.

Well then we hear wrong. Serotonin, or 5-Hydroxytryptamine, along with its respective family of functionally diverse receptors (5HT1-5HT7), is associated primarily with sensory perception, regulation of arousal, certain aspects of cognition/memory, mood, and hormonal regulation, among a few other essential biological functions. Simply increasing extracellular levels of this hormone alone typically causes [if anything at all] any of: anxiety, dizziness, gastric effects (diarrhea/constipation), hypertension, mild sedation, alternate cognitive impairment or enhancement, and sexual dysfunction.

So does this mean that MDAI has effects other than simply causing serotonin release? And similarly for MDMA, what does it do apart from stimulating NE/DA/Serotonin release?
What do you mean by "extracellular levels", in particular? Is that not what these drugs affect?

And by the way, I have to ask - why do all drug users with access Google nowadays consider themselves amateur neuroscientists?

Would you rather I don't read scientific papers?

Sorry the New Age websites got to you before skepticism and scientific inquiry...

Don't worry, the new-age websites certainly haven't "got to me" - I wouldn't trust them for a second.

Edit: fixed quotations

 

[its.euphoric]

I think because of the mdma damage, your body is trying to repair itself more so it's trying to get more Rem sleep.

And what do you mean an increase in the 3? Ssri's keep serotonin in the synpase for longer, only serotonin. The reason why some can't sleep I think is because there's an increase in serotonin which blocks the usual increase in melatonin when you're gonna go to sleep.

 

[P A]

So does this mean that MDAI has effects other than simply causing serotonin release?

Not that I'm aware of, although if the anecdotal reports of pharmacalogically unexpected/unexplainable effects continue [along with current trends of escalating awareness and use], I'm sure more mechanistic research will be justified. On the other hand, anecdotal 'evidence' is worth jack shit to rigorous scientists interested more in molecular interactions and well-designed studies than subjective responses among a bunch of idiosyncratic drug users in uncontrolled circumstances posting their experiences on the internet. In other words, no, to my knowledge, MDAI is a highly selective vesicular serotonin releaser and nothing more; typically requiring coadministration of dopaminergic amphetamines to produce effects comparable to MDMA - a relatively potent dopamine/noradrenaline releaser in its own right, though a bit weaker in that regard than its serotonergic activity.

Besides the popular mechansim of serotonin release, MDMA is a potent agonist at the postsynaptic 5-HT1A receptors, and requires 5-HT2B receptor activation to maintain its effects on extracellular serotonin levels. This, among other disparate actions [usually involving receptor agonism], brands MDMA as a truly complex drug, the subjective effects of which cannot be narrowed down to a single mechanism, but rather a complex combination of all of them.

Would you rather I don't read scientific papers?

Read whatever you like. I'm in full support of independent research (I do it every day), but if you're going to be reading contemporary neuroscience journals, you're necessarily going to be interpreting the information therein within the context of previously acquired information - or misinformation. Going into a published abstract with the idea that serotonin is "HaPpee cHemikale guise!11" will render you near-completely unable to effectively interpret what you're reading. Get the basics first, preferably by way of a half-decent source [Wikipedia: I'm not kidding], then move on to the more rocky territory of professional biochem research. I don't mean to be a patronizing asshole, but see my above post for frustrated rants regarding the disease of misinformation and virulent internet bullshit.

Don't worry, the new-age websites certainly haven't "got to me" - I wouldn't trust them for a second.

It's a good thing. Don't let your guard down - their gypsy pseudoscience is insidious.

All apologies for the pissy, pedantic posts, but this New Age monoamine shit works me into righteous internet anger.

 

[Slapdragonx]

Zoloft blocks a full night's sleep IME, normally I wake up atleast once, sometimes 3 times. Always with insanely vivid dreams that are quite awesome.

 

[KAYLA2010]

I did not write the "new age" comment.....I believe that REM is affected by a choline (precursor) deficiency acetylcholine deficiency..whatever you want to call it.............also light (sensor behind retina I think..well im pretty sure anyways), stress and other stimulating things can cause melatonin levels to drop so you wouldn't have as much of the hormone made by your pineal gland to stimulate your GABA receptors...so you would not be as tired at night also you would have trouble falling/staying asleep(REM is effected).....

If this is not right someone correct me because I am about to go research this right now....just to make sure....because I don't remember exactly..

Also serotonin think of it more as a over all well being neuro......

 

[P A]

I did not write the "new age" comment

No, you're right. You didn't. I did...

I believe that REM is affected by a choline (precursor) deficiency acetylcholine deficiency

An "acetylcholine deficiency" would leave you in one of two sates - fully paralytic or dead [probably from a cardiac syndrome, but who knows what wacky shenanigans such a ridiculous disorder could cook up?]. Your body requires cholinergic transmission for a lot more than just REM sleep and thinking, and there are quite a few neurons outside of your brain as well. See my posts on New Age "[insert neurotransmitter] reductionism." I'm done raging.

Also serotonin think of it more as a over all well being neuro......

My academically pompous teeth clench. Again, see my above posts.

 

[I NUK3D U]

@OP

I suppose understanding the difference between REM sleep, and simply being non-conscious, is an important starting point in beginning to understand this somewhat wide and complex topic.

 

[KAYLA2010]

No, you're right. You didn't. I did...



An "acetylcholine deficiency" would leave you in one of two sates - fully paralytic or dead [probably from a cardiac syndrome, but who knows what wacky shenanigans such a ridiculous disorder could cook up?]. Your body requires cholinergic transmission for a lot more than just REM sleep and thinking, and there are quite a few neurons outside of your brain as well. See my posts on New Age "[insert neurotransmitter] reductionism." I'm done raging.



My academically pompous teeth clench. Again, see my above posts.

Since I don't know much about serotonin then whatever you said above prob right(i have not read what you said yet)....

Ok well maybe im wrong about the deficiency (meanings choline (precusor) acetylcholine but I could have swore it could be a cause of people have autonomic nervous system dysfunction, fybromialgia, misdiagnosis of panic attacks etc........

Also studies show that most people are actually deficient in their intake there intake of choline.....

You really need to look into it before just downing something I say....As i said before these are just my own thoughts......after my own research....

If just drives me insane for you to just basically say there is no such thing and basically tell me I have to be retarded to come up with an answer like that..I read way to much .........

So now I hope that you read your post then my answer again and then you will get it.....hopefully.

 

[Moredopamine]

As it has been pointed out, the monoamine network does not work like this at all. 5ht2c receptor agonists actually induce anxiety rather than "warmth and empathy." The receptors are found in denser quantities in the PFC of post-mortem suicide patients. Unsurprisingly, therefore, agomelatine, a 5ht2c antagonist, has antidepressant properties.

Tianeptine, a selective serotonin reuptake enhancer, "paradoxically" has anxiolytic and anti-deppressant effects--clearly depression =/= a raw "serotonin deficiency."

I have to ask - why do all drug users with access Google nowadays consider themselves amateur neuroscientists?

Just so you know, so-called 'monoamine reductionism' is nothing more than a tired media ploy invented for the sole purpose of dishonestly persuading hapless consumers by appealing to their ignorance and gullibility. Depression is NOT a serotonin deficiency. Feeling tired is NOT symptomatic of "low dopamine levels," whatever the fuck that's even supposed to mean. And selective noradrenaline reuptake inhibitors don't wake you up. Shocking? The brain is a multifarious, highly complex facet of study, and referring to serotonin as being "associated with empathy and warmth" does nothing to further others' understanding (and in many cases likely hinders it). Just type 'serotonin' and 'sleep' into Pubmed for christ's sake.

And yeah, I know, you didn't actually mention any of the above fallacies, but you might as well have. Sorry the New Age websites got to you before skepticism and scientific inquiry...

I just have to say, I love you good sir! "Monoamine reductionism?"--fantastic.

Reminds of a time a friend of mine took the good initiative to explain to me that MDMA "makes you feel great" because it gives you "serotonin" and that it "releases all your endorphins."

I know it's silly to expect people to have some quasi-technical understanding of the brain but for shit's sake don't go spewing on about such an utterly complex and yet-to-be understood organ as if you've a Ph.D in the field! (and I'm not aiming this at the OP/anyone in this thread--just a general rant)

 

[KAYLA2010]

Not that I'm aware of, although if the anecdotal reports of pharmacalogically unexpected/unexplainable effects continue [along with current trends of escalating awareness and use], I'm sure more mechanistic research will be justified. On the other hand, anecdotal 'evidence' is worth jack shit to rigorous scientists interested more in molecular interactions and well-designed studies than subjective responses among a bunch of idiosyncratic drug users in uncontrolled circumstances posting their experiences on the internet. In other words, no, to my knowledge, MDAI is a highly selective vesicular serotonin releaser and nothing more; typically requiring coadministration of dopaminergic amphetamines to produce effects comparable to MDMA - a relatively potent dopamine/noradrenaline releaser in its own right, though a bit weaker in that regard than its serotonergic activity.

Besides the popular mechansim of serotonin release, MDMA is a potent agonist at the postsynaptic 5-HT1A receptors, and requires 5-HT2B receptor activation to maintain its effects on extracellular serotonin levels. This, among other disparate actions [usually involving receptor agonism], brands MDMA as a truly complex drug, the subjective effects of which cannot be narrowed down to a single mechanism, but rather a complex combination of all of them.



Read whatever you like. I'm in full support of independent research (I do it every day), but if you're going to be reading contemporary neuroscience journals, you're necessarily going to be interpreting the information therein within the context of previously acquired information - or misinformation. Going into a published abstract with the idea that serotonin is "HaPpee cHemikale guise!11" will render you near-completely unable to effectively interpret what you're reading. Get the basics first, preferably by way of a half-decent source [Wikipedia: I'm not kidding], then move on to the more rocky territory of professional biochem research. I don't mean to be a patronizing asshole, but see my above post for frustrated rants regarding the disease of misinformation and virulent internet bullshit.



It's a good thing. Don't let your guard down - their gypsy pseudoscience is insidious.

All apologies for the pissy, pedantic posts, but this New Age monoamine shit works me into righteous internet anger.

I am wondering what you got out of my response......I was saying think of serotonin as a over all well being neuro...BEcause everyone seems to think it makes you happy......I just was not going to explain it all because then when someone doesn't know much at all about serotonin and you go into detail you lose them.....So i just said well being meaning just ok instead of happy feelings.......serotonin.....wait i already said this anyways.....I am on this website for learning and information for my own benefit because I would not feel comfortable going to a doctor and asking some of the questions I have.........I remember reading your post last night and thinking wow i found someone who knows serotonin is not a happy drug........and most of the time I just can't find the words to say when posting........so I just try and make a summary of everything I am thinking and sometimes i sum up to much and thats what gave you the impression I don't know anything about serotonin.......I do like critisism just why do you keep writing "pissy, pedantic posts" your words.......just write a summary of how you think i am wrong and why and I will learn from it......

 

[P A]

Also studies show that most people are actually deficient in their intake.....

Jesus christ. You cannot be "deficient" in serotonin, as it is not an essential nutrient. You do not eat serotonin. Do I need to provide references for this?

I know it's silly to expect people to have some quasi-technical understanding of the brain but for shit's sake don't go spewing on about such an utterly complex and yet-to-be understood organ as if you've a Ph.D in the field!

THANK YOU. Loving fuck, at least someone around here agrees with me. But if you'll let me, I think I'll change 'a Ph.D' to 'a basic level of comprehension.'

I remember reading your post last night and thinking wow i found someone who knows serotonin is not a happy drug........and most of the time I just can't find the words to say when posting

.I do like critisism just why do you keep writing "pissy, pedantic posts" your words

I apologize if I offended you, but I honestly don't know how to respond. Just to be clear, none of my "pissiness" was directed at you in particular, and I certainly don't want to exclude anyone from discussion. However, you seem to have [and, yeah, I know I sound like an utter douche for saying this] a LOT of learning to do. Yes, I KNOW that over 9000 websites (and magazine articles, and Youtube, and prescription drug commercials) spew the usual shit about serotonin and its link to depression, anxiety, and other disorders of mentation, but the actual information bestowed upon the consumer is generally little more than half-truth marketing bilge based on either decades-outdated hypotheses or outright pseudoscience; and you, the consumer, are in turn reproducing a sizable portion of this (mis)information in your posts. This isn't anything personal, it's just a matter of basic comprehension of concepts that have been sufficiently twisted by "the media" to the point of being made unrecognizable by any contemporary neuroscientist born after 1980.

Your posts are agrammatic, erratic, full of ellipses, and devoid of legible syntax. Now this isn't to say that I'm Mr. Ernest Fucking Hemingway himself, but I usually put sincere effort into composing words, either in speech or print, in order to ease the burden of understanding on others as much as humanly possible. In other words, I try to make it as easy as possible for someone with knowledge of both the English language and the subject matter at hand to understand what I'm trying to say. Clarity is my first priority in speech and writing, and I think anyone literate should make that their primary linguistic goal as well - after all, this is our only form of effective, sophisticated communication among others in our species. And to be blunt: given that I find your posts inscrutable and pretty damn difficult to read, I'm going to have a habit of dismissing or ignoring what you say, regardless of whether it happens to have merit, simply because I either A) Do not understand you OR B) Don't have time to analyze your hopelessly cryptic style of writing, making me unable to effectively respond. This isn't intended as an insult, but I really don't know how else to put this. You write the way most people think, or in some cases talk - in detached, heterogeneous phrases not clear in meaning to anyone but yourself (or perhaps a cryptographer).

By the way - having a bit of an interest in language, I never dreamed I would see the equivalent of an internet accent before, but you've honestly changed all that for me. For that, thanks...I guess.

basically tell me I have to be retarded to come up with an answer like that..I read way to much .........

You said this. Not me.

 

[KAYLA2010]

Jesus christ. You cannot be "deficient" in serotonin, as it is not an essential nutrient. You do not eat serotonin. Do I need to provide references for this?



THANK YOU. Loving fuck, at least someone around here agrees with me. But if you'll let me, I think I'll change 'a Ph.D' to 'a basic level of comprehension.'





I apologize if I offended you, but I honestly don't know how to respond. Just to be clear, none of my "pissiness" was directed at you in particular, and I certainly don't want to exclude anyone from discussion. However, you seem to have [and, yeah, I know I sound like an utter douche for saying this] a LOT of learning to do. Yes, I KNOW that over 9000 websites (and magazine articles, and Youtube, and prescription drug commercials) spew the usual shit about serotonin and its link to depression, anxiety, and other disorders of mentation, but the actual information bestowed upon the consumer is generally little more than half-truth marketing bilge based on either decades-outdated hypotheses or outright pseudoscience; and you, the consumer, are in turn reproducing a sizable portion of this (mis)information in your posts. This isn't anything personal, it's just a matter of basic comprehension of concepts that have been sufficiently twisted by "the media" to the point of being made unrecognizable by any contemporary neuroscientist born after 1980.

Your posts are agrammatic, erratic, full of ellipses, and devoid of legible syntax. Now this isn't to say that I'm Mr. Ernest Fucking Hemingway himself, but I usually put sincere effort into composing words, either in speech or print, in order to ease the burden of understanding on others as much as humanly possible. In other words, I try to make it as easy as possible for someone with knowledge of both the English language and the subject matter at hand to understand what I'm trying to say. Clarity is my first priority in speech and writing, and I think anyone literate should make that their primary linguistic goal as well - after all, this is our only form of effective, sophisticated communication among others in our species. And to be blunt: given that I find your posts inscrutable and pretty damn difficult to read, I'm going to have a habit of dismissing or ignoring what you say, regardless of whether it happens to have merit, simply because I either A) Do not understand you OR B) Don't have time to analyze your hopelessly cryptic style of writing, making me unable to effectively respond. This isn't intended as an insult, but I really don't know how else to put this. You write the way most people think, or in some cases talk - in detached, heterogeneous phrases not clear in meaning to anyone but yourself (or perhaps a cryptographer).

By the way - having a bit of an interest in language, I never dreamed I would see the equivalent of an internet accent before, but you've honestly changed all that for me. For that, thanks...I guess.



You said this. Not me.

I never said anything about serotonin deficiency what are you talking about? I said choline...........wow I don't know what your talking about.......THen in the other post you sent me a link I have already read explaining what i already was saying.........???

 

[KAYLA2010]

Jesus christ. You cannot be "deficient" in serotonin, as it is not an essential nutrient. You do not eat serotonin. Do I need to provide references for this?

I do find you very offensive---If you read what you wrote about "acetylocholine deficiency" you would then remember and see why I wrote inadequate intake.....(I was talking about choline)....wth nothing to do with serotonin

(new age quote from article for you)

Choline has only recently been recognized as an essential nutrient. Choline is part of the neurotransmitter acetylcholine, which plays a major role in the brain; for this reason, many studies have been designed to look at choline's role in brain function.

Choline functions as a part of a major biochemical process in the body called methylation; choline acts as a methyl donor. Until recently, it was thought that the body could use other substances to substitute for choline, such as folate, vitamins B6 and B12, and the amino acid methionine. But recent evidence has finally shown that, for some people, adequate choline supplies cannot be maintained by other nutrients and must be obtained independently through diet or supplements.1-3

 

[libc.so.5]

I did not write the "new age" comment.

Yeah, sorry, I made a mistake with the quoting - it was P A who said that.

I think because of the mdma damage, your body is trying to repair itself more so it's trying to get more Rem sleep.

It seems that there are significant effects without MDMA at all - one of the studies I linked to involved putting people on diets deficient in tryptophan, causing a serotonin decrease that way.

And what do you mean an increase in the 3? Ssri's keep serotonin in the synpase for longer, only serotonin.

Well, I meant that the impression and intuition that I had was that "increase in brain activity == decrease in sleep" - it seems that this is completely wrong.

As it has been pointed out, the monoamine network does not work like this at all. 5ht2c receptor agonists actually induce anxiety rather than "warmth and empathy." The receptors are found in denser quantities in the PFC of post-mortem suicide patients. Unsurprisingly, therefore, agomelatine, a 5ht2c antagonist, has antidepressant properties.

Besides the popular mechansim of serotonin release, MDMA is a potent agonist at the postsynaptic 5-HT1A receptors, and requires 5-HT2B receptor activation to maintain its effects on extracellular serotonin levels. This, among other disparate actions [usually involving receptor agonism], brands MDMA as a truly complex drug, the subjective effects of which cannot be narrowed down to a single mechanism, but rather a complex combination of all of them.

Would it be fair, though, to say that the activation of particular receptors (5-HT2A/5-HT2B?) could be largely implicated in the production of desirable empathogenic effects? Wikipedia only lists 5-HT2B as being agonised by MDMA, but doesn't say that 5-HT2B affects mood. When you say MDMA "requires 5-HT2B receptor activation", do you mean that it doesn't activate these by itself?
I've got lots of reading to do - I think it's quite easy to skim over these articles and get the wrong impression of what's going on. I don't mean to over-simplify the mechanics of the brain at all.

Not that I'm aware of, although if the anecdotal reports of pharmacalogically unexpected/unexplainable effects continue [along with current trends of escalating awareness and use], I'm sure more mechanistic research will be justified. On the other hand, anecdotal 'evidence' is worth jack shit to rigorous scientists interested more in molecular interactions and well-designed studies than subjective responses among a bunch of idiosyncratic drug users in uncontrolled circumstances posting their experiences on the internet. In other words, no, to my knowledge, MDAI is a highly selective vesicular serotonin releaser and nothing more; typically requiring coadministration of dopaminergic amphetamines to produce effects comparable to MDMA - a relatively potent dopamine/noradrenaline releaser in its own right, though a bit weaker in that regard than its serotonergic activity.

What unexpected/unexplainable effects are you referring to, specifically? I've seen others mention that combining with DA/NE releasers may produce MDMA-like effects... I wouldn't be at all surprised to see users move in this direction if they can't get real MDMA. There would also be more scope for tailoring the effects to your wishes by changing the ratios.

...over 9000 websites...

lol

@OP

I suppose understanding the difference between REM sleep, and simply being non-conscious, is an important starting point in beginning to understand this somewhat wide and complex topic.

Great, now I'm going to end up spending another 4 hours clicking all the links on wikipedia


I found this [URL="http://en.wikipedia.org/wiki/Neurotransmitter#Excitatory_and_inhibitory]interesting paragraph[/URL]:

Some neurotransmitters are commonly described as "excitatory" or "inhibitory". The only direct effect of a neurotransmitter is to activate one or more types of receptors. The effect on the postsynaptic cell depends, therefore, entirely on the properties of those receptors. It happens that for some neurotransmitters (for example, glutamate), the most important receptors all have excitatory effects: that is, they increase the probability that the target cell will fire an action potential. For other neurotransmitters (such as GABA), the most important receptors all have inhibitory effects. There are, however, other neurotransmitters, such as acetylcholine, for which both excitatory and inhibitory receptors exist; and there are some types of receptors that activate complex metabolic pathways in the postsynaptic cell to produce effects that cannot appropriately be called either excitatory or inhibitory. Thus, it is an oversimplification to call a neurotransmitter excitatory or inhibitory—nevertheless it is so convenient to call glutamate excitatory and GABA inhibitory that this usage is seen very frequently.

I never really considered the existence of inhibitory receptors.

 

[P A]

What unexpected/unexplainable effects are you referring to, specifically?

Unexpected effects of a vanilla serotonin releaser include euphoria, empathogenesis, 'stimulatory' or 'arousing' effects, among others commonly attributed to drugs of much greater pharamcologic sophistication and appropriately localized activity (i.e. dopamine system, peptide modulation, etc.) than MDAI. The true appeal in the aminoindanes is their conspicuous lack of degenerative systemic toxicity observed even in cases of extreme dosing in rats.

When you say MDMA "requires 5-HT2B receptor activation", do you mean that it doesn't activate these by itself?

Nonono. It most certainly does. What I mean by this: 5-HT2B receptor agonism plays such an important role in MDMA's effects that deactivation of the receptor by a competitive antagonist neutralizes the majority of the drug's discriminative stimulus properties that distinguish it from other drugs of abuse. The 5-HT2B receptors play an integral role in the regulation of serotonergic tone via their allosteric modualtion of the serotonin transporter, the inhibition of which occurs following potent activation of the receptor, something MDMA must do in order to induce further downstream alterations in neural function that give it's unique status among most other drugs in its class (psychostimulants). So to clear up any potential confusion, just about every serotonin receptor subtype has some role in the regulation of consciousness and emotion, the 5-HT2B variety standing out as a good example of a ligand site whose actions are diverse yet potent, especially with regard to drug psychoactivity.

I never really considered the existence of inhibitory receptors.

Then I guess you have quite a bit of reading to do. Lawl.

Choline functions as a part of a major biochemical process in the body called methylation; choline acts as a methyl donor.

Aside from its DNA-regulating and histone-modifying properties, choline does not exert significant influence on methylation-dependent systems [in the CNS] when compared to the major players adenosylmethionine, cobalamin, and methylfolate. Furthermore, neuronal transmethylation and its influence on monoamine neurotransmitter synthesis is generally tightly regulated in the presence of sufficient quantities of B vitamins and amino acids, and is very unlikely to be significantly altered by administration of a compound that can't even cross the blood-brain barrier in meaningful concentrations. Choline may be an essential nutrient, but this -

Choline functions as a part of a major biochemical process in the body called methylation; choline acts as a methyl donor

has nothing to do with this -

Choline is part of the neurotransmitter acetylcholine, which plays a major role in the brain

Choline is both a dietarily essential DNA methyl donor and a precursor to the neurotransmitter acetylcholine. These two functions are mechanistically independent and biochemically unrelated. You're talking about two completely different things, neither of which, by the way, were mentioned in any of your posts in other threads. To reiterate, you cannot be deficient in neurotransmitters as they are not essential nutrients. The only time the word "deficiency" would be remotely applicable would be under highly unique circumstances [e.g. dietary tryptophan depletion in a laboratory setting or following carcinoid syndrome] not relevant to 99.9% of the population. Dietary administration of choline in controlled trials has failed to significantly elevate levels of acetylcholine in the brain. Nor, I expect, would it have considerable (if any) impact upon DNA methylation, as this process is, as mentioned above, tightly regulated for obvious reasons.

Also KAYLA, I tend to use the shorthand 'choline' when referring to acetylcholine in discussions of so-called 'cholinergic' drug effects (that is, drugs that exert influence over the acetylcholine system). Choline and acetylcholine are frequently (and confusingly) used interchangeably, though when used in this context, they invariably refer specifically to the neurotransmitter acetylcholine, not the dietary precursor. Sorry for any fuckup/confusion that may have caused.

 

[KAYLA2010]

My actual point in this specific post about sleep was to answer his question about (REM)sleep........

The most important thing is to give the poster of this thread the most information of what I think.
I did not do the best job of explaining so This is more detail....
so he can better understand How reducing a choline decifiency can help your REM sleep.

ACh-the most important inducer of REM sleep because it effects your biological clock...let me break it all down......
with out summing anything up, So that everyone can understand exactly what I am trying to interpret from my brain.

Choline is a very important nutrient...

Choline- compound that is used by the body to synthesize(bind) acetylcholine(neurotransmitter)
Acetylcholine--is a chemical compound meaning- (more than one compound makes up this neurotrasmitter.)
Acetylcholine if the number one neurotransmitter in all autonomic ganglia.
(ACh<--I will use the abbr. for acetylcholine b/c the word to long to keep writing it LOL)

Choline-one of two components of ACh, very important for the nervous system function.
Second component of ACh is ester of acetic acid.
By the way Chloragenic means related to the neurotransmitter acetylcholine.
Anyways..... ACh is made when combining ester of acetic acid and choline.

But just to make this a little more complicated (PA I know this makes you happy) I will go into more detail....

FIrst we need Thioester to happen (combining ester of acetic acid with coenzyme a = acetyl-CoA (acetyl+coenzyme A)
Thioester means combining an organic acid with a enzyme....
Then in the process acetic acid has a proton taken away resulting in = acetate

choline acetyltransferase(organic enzyme) joins together the acetate and choline.
((((Ok Now wahhh Bamm neurotransmitter "acetylcholine(ACh)" is made.))))
ACh- functions- peripheral nervous system (ANS,SNS..etc..)
ACh is a "major" neurotransmitter in the autonomic nervous system.
ACh-has an important role in the enhancement of sensory perceptions<--Important! (for REM, attention, anything regulated by your internal clock AKA autonomic nervous system.....
Sensory perceptions....Are controled by your Autonomic Nervous System

QUOTED from somewhere-->Damage to the cholinergic (acetylcholine-producing) system in the brain is related to memory deficits.
Quote from WIKI-Acetylcholine is the preganglionic neurotransmitter for both divisions of the ANS, as well
as the postganglionic neurotransmitter of parasympathetic neurons. Nerves that release acetylcholine are said to be cholinergic.
In the parasympathetic system, ganglionic neurons use acetylcholine as a neurotransmitter, to stimulate muscarinic receptors.
http://en.wikipedia.org/wiki/Autonomic_nervous_system

(reason for my Dysautonomia (autonomic nervous system disorder.. comment in my other post)

Also plays a part in the central nervous system as a (neuromodulator).
neuromodulator- process where your neurotransmitters regulate neurons. Neurons-AKA-nerve cell) regulate by releasing chemicals (chemicals with a job)

ACh uses its """cholinergic system""" to enhance the excitatory/inhibitory(arousal and reward) responses of the receptors in the NS.

ACh receptors= Protiens that are a stuck together to help with binding of the ACh neurotransmitter.
"""Cholinergic system" is the use of the acetylcholine receptors. Those receptors are there because of the ACh neurotransmitter..derived from Choline....

ACh receptors(AChR)- nicotinic acetylcholine receptors (nAChR)
(this is the recceptor that is inhibited by PCP which causes damage a little research and i answer my own question but..
it would have been really really nice if someone had just posted it..also It can be reversed...I explained that somewhere already)

Anyways the other major AChR is muscarinic acetylcholine receptors (mAChR)..
BOth of thoughs receptors are the main kinds of cholinergic receptors.(again..cholinergic means part of ACh neurotransmitter)
ACh as a neuromodulator(using its cholinergic system) for arousal and reward in the nervous system.^--remember enhances the response of receptors.


(Why would the fda still make manufactures of baby formula add choline?)
So now with me helping out and being more detailed.....
The reason I feel a deficiency of the nutrient Choline is because )))with out it non of this can happen...Also.......
If you do not have enough Choline or you have damaged a receptor made from Choline.........
Your autonomic clock (autonomic nervous system)--that is controled by your ACh neurotransmitter....Will not work properly which I feel and
research, studies, MD journals.....all show that this could be a major problem with a whole lot of people....And would be one of the major
neurotransmitters affecting REM sleep........................

Can you imagine what is going on with the people with this problem....
))))A dysfunction so small somewhere,somehow in your PNS/CNS((....especially if your problem is caused by voluntary drug use.....

PA Now do I make enough sense for you to understand? I know someone will think this is a specific to make my point........

I have to add-- choline supplement that can cross the BBB- Acetyl-L-carnitine

 

[onmyway]

wow, it is hot in here.


KAYLA2010: after reading the above post, i think you don't quite understand some of the basic tenets of neurochemistry you are obviously a smart person but you should definitely do some more reading about the basics. concepts like receptors, ligands, biochemical pathways of the basic neurotransmitters, neurophysiology, etc...

im not trying to flame you or anything, but when you write long posts and argue with people your lack of knowledge will be quickly exposed because there ARE experts here (i am not one of them).

on the other hand, this is a great place to learn. in fact there is a pretty cool thread that outlines many of the basics:

http://www.bluelight.ru/vb/showthread.php?t=166687

i still reference it from time to time, even though i have learned all that stuff during my formal education. its a great resource.