Is jaw clenching caused by serotonin?

[ebola?]

Oddly, I only seem to experience bruxism in response to trimonoamine releasers, not classical stimulants or selective SRAs.

ebola

 

[serotonin2A]

Motoneurons in the facial and trigeminal nuclei (as well as other cranial nerve nuclei) contain large numbers of 5-HT2A receptors, and activation of the receptors depolarizes the neurons and increases their excitability. This is one of the things that causes bruxism. Look up some of George Aghajanian's studies, although several other groups have studied how serotonin influences motorneuron membrane properties and firing, including spinal motoneurons. Dopamine and norepinephrine may also play a role in the response to MDMA but direct and indirect 5-HT2A receptor activation is the primary mechanism.

(about the earlier post about the basal ganglia and bruxism) The basal ganglia is involved in habits, among other things. So the direct and indirect pathways come into play with bruxism where someone is habitually grinding their teeth and cannot stop. But it is much more likely that MDMA is acting at the level of motoneurons to induce bruxism.

 

[crOOk]

Motoneurons in the facial and trigeminal nuclei (as well as other cranial nerve nuclei) contain large numbers of 5-HT2A receptors, and activation of the receptors depolarizes the neurons and increases their excitability.

Thank you! I tried to find out about how easily the motoric fibers of the trigeminal nerve could be depolarized by serotonergic activity alone, but couldn't find any info, probably because I didn't take enough time to do so. Are you sure this is true? Could you link some sources for the things you've said?

It would seem quite obvious that depolarization of the efferent trigeminal nerve fibers via 5htr's would be the most direct route, but I wonder why I haven't found this stated anywhere. There are literally thousands of articles on bruxism and hundreds of reviews (no shit!), but I found no mention of this rather obvious pathomechanism. Maybe I just didn't check thoroughly enough? Would be cool if you could link some sources. I will be looking into some articles by George Aghajanian, maybe that clears it up.

EDIT: I found 28 of his articles, but none of them mention bruxism in the title or abstract. Could you please specify which one you were referring to?

EDIT: Can anyone send me the full article? I don't have access to that journal for issues published after 2009. http://www.ncbi.nlm.nih.gov/pubmed/25195948

EDIT: Searching for 'bruxism 5ht2a' on pubmed yields zero results...

 

[crOOk]

Found another article on this. It pretty much confirms what you said, but also extends it to norepinephrinergic activation of motoric trigeminal fibers.

Abstract

In animals, sodium- and calcium-mediated persistent inward currents (PICs), which produce long-lasting periods of depolarization under conditions of low synaptic drive, can be activated in trigeminal motoneurons following the application of the monoamine serotonin. Here we examined if PICs are activated in human trigeminal motoneurons during voluntary contractions and under physiological levels of monoaminergic drive (e.g., serotonin and norepinephrine) using a paired motor unit analysis technique. We also examined if PICs activated during voluntary contractions are larger in participants who demonstrate involuntary chewing during sleep (bruxism), which is accompanied by periods of high monoaminergic drive. In control participants, during a slowly increasing and then decreasing isometric contraction, the firing rate of an earlier-recruited masseter motor unit, which served as a measure of synaptic input to a later-recruited test unit, was consistently lower during derecruitment of the test unit compared with at recruitment (ΔF = 4.6 ± 1.5 imp/s). The ΔF, therefore, is a measure of the reduction in synaptic input needed to counteract the depolarization from the PIC to provide an indirect estimate of PIC amplitude. The range of ΔF values measured in the bruxer participants during similar voluntary contractions was the same as in controls, suggesting that abnormally high levels of monoaminergic drive are not continually present in the absence of involuntary motor activity. We also observed a consistent “onion skin effect” during the moderately sized contractions (<20% of maximal), whereby the firing rate of higher threshold motor units discharged at slower rates (by 4–7 imp/s) compared with motor units with relatively lower thresholds. The presence of lower firing rates in the more fatigue-prone, higher threshold trigeminal motoneurons, in addition to the activation of PICs, likely facilitates the activation of the masseter muscle during motor activities such as eating, nonnutritive chewing, clenching, and yawning.

[...]

In addition, trigeminal motoneurons receive direct serotonergic inputs from the nuclei raphe obscurus, raphe pallidus, and raphe dorsalis [1;2] [these nuclei release serotonin; they are not part of the trigeminal nucleus, but I am pretty sure they are connected to the trigeminal nucleus], as well as norepinephrine inputs from the locus subcoerulus, A5 and A7 cells, and sparse innervation from the locus coeruleus [3;4;5].

Similar to motoneurons innervating the limb muscles, trigeminal motoneurons display bistable membrane properties such as plateau potentials and burst oscillations where long-lasting periods of depolarization can occur under low levels of synaptic drive [6]. These properties are mediated by voltage-activated, sodium and calcium persistent inward currents (PICs) that are, in turn, facilitated by serotonin and norepinephrine receptors located on the motoneuron [7]. For example, application of serotonin can induce a negative slope region in the current-voltage relationship of trigeminal motoneurons that is subsequently abolished when the persistent L-type Ca2+ and Na+ currents are blocked with nimodipine and tetrodotoxin, respectively [8;6]. Given the demonstration of strong PIC activation in animals, we examined if trigeminal motoneurons in the human also exhibit indirect evidence of PIC activation by using a paired motor unit analysis technique developed for limb muscles [9]. Evidence for PIC activation, namely motor unit activity that persists under levels of synaptic drive lower than that needed to initially recruit the motor unit (i.e., self-sustained activity), was examined during isometric, voluntary contractions onto a bite bar [10].

Interestingly, the discharge of neurons in the raphe nuclei, locus coeruleus, subcoeruleus, and A5/A7 cells, which release PIC-facilitating serotonin and norepinephrine to the trigeminal motoneuron pool, increases during microarousals [11;12;13]. Individuals with bruxism experience increased numbers of microarousals during sleep (Kato et al. 2001, 2003, 2011) and likely increases in monoaminergic drive to trigeminal motoneurons. Thus we examined with paired motor unit analysis if participants with bruxism display larger estimates of PIC amplitude during voluntary contractions compared with nonbruxing controls to determine if tonically elevated levels of monoaminergic drive to trigeminal motoneurons are present in bruxters, even in the absence of microarousals and rhythmic masticatory muscle activity.

[...] [I will leave out the methods and results and go straight to:]

Discussion

Unlike the animal experiments recorded in vitro, there is likely sufficient endogenous levels of serotonin and/or norepinephrine in the awake human to allow for activation of PICs during voluntary contractions. Excessive monoaminergic drive to trigeminal motoneurons was likely not present in the awake Brux participants, who present with involuntary chewing and teeth clenching during sleep, as indicated by estimates of PIC amplitudes that were similar to the NBrux controls. [...] after recruitment of a PIC, the firing rate of a motoneuron is linearly related to the injected or synaptic current it receives [17;18;9;8;6].

[...]

The presence of involuntary chewing and teeth clenching that occur during sleep in the Brux participants is not associated with abnormally large PICs activated during voluntary contractions under awake conditions. It may be that large PICs are only present during periods of involuntary chewing and teeth clenching given that these involuntary motor behaviors occur during periods of microarousals when monoaminergic drive to the trigeminal motoneuron pool is high [11;12;13]. In line with this, drugs such as amphetamine and serotonin reuptake inhibitors, which increase levels of norepinephrine and serotonin, respectively, increase episodes of involuntary activity in Brux participants [19;20] and the amplitude of PICs in limb motoneurons [21;10]. Thus the amplitude of PICs should, in future studies, be estimated during sleep when involuntary muscle activity is present

[-> The last word on this has yet to be spoken]



1 http://www.ncbi.nlm.nih.gov/pubmed/7685070 An immunocytochemical and autoradiographic investigation of the serotoninergic innervation of trigeminal mesencephalic and motor nuclei in the rabbit
2 http://www.ncbi.nlm.nih.gov/pubmed/8264992 The sites of origin of serotoninergic afferent fibers in the trigeminal motor, facial, and hypoglossal nuclei in the rat
3 http://www.ncbi.nlm.nih.gov/pubmed/12235046 A5 cells are silenced when REM sleep-like signs are elicited by pontine carbachol
4 http://www.ncbi.nlm.nih.gov/pubmed/1702107 Nuclei of origin of monoaminergic, peptidergic, and cholinergic afferents to the cat trigeminal motor nucleus: a double-labeling study with cholera-toxin as a retrograde tracer
5 http://www.ncbi.nlm.nih.gov/pubmed/20217366 Noradrenergic control of trigeminal motoneurons in sleep: relevance to sleep apnea
6 http://www.ncbi.nlm.nih.gov/pubmed/9636091 Ionic basis for serotonin-induced bistable membrane properties in guinea pig trigeminal motoneurons
7 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2655409/ Noradrenaline triggers muscle tone by amplifying glutamate-driven excitation of somatic motoneurones in anaesthetized rats
8 http://www.ncbi.nlm.nih.gov/pubmed/9212246 Multiple effects of serotonin on membrane properties of trigeminal motoneurons in vitro
9 http://www.ncbi.nlm.nih.gov/pubmed/15342360 Role of motoneurons in the generation of muscle spasticity after spinal cord injury
10 http://www.ncbi.nlm.nih.gov/pubmed/4353259 Firing rate of individual motor units in voluntary contraction of abductor digiti minimi muscle in man
11 http://www.ncbi.nlm.nih.gov/pubmed/10036262 Physiological properties of raphe magnus neurons during sleep and walking
12 http://www.ncbi.nlm.nih.gov/pubmed/11457597 Differentiation of presumed serotonergic dorsal raphe neurons in relation to behaviour and wake-sleep states
13 http://www.ncbi.nlm.nih.gov/pubmed/20542093 Locus coeruleus neuronal activity during the sleep-waking cycle in mice
14 http://www.ncbi.nlm.nih.gov/pubmed/11706956 Sleep bruxism: an oromotor activity secondary to microarousal
15 http://www.ncbi.nlm.nih.gov/pubmed/12651932 Evidence that experimentally induced sleep bruxism is a consequence of transient arousal
16 http://www.ncbi.nlm.nih.gov/pubmed/22205593 Masseter EMG activity during sleep and sleep bruxism
17 http://www.ncbi.nlm.nih.gov/pubmed/11600653 Plateau potentials in sacrocaudal motoneurons of chronic spinal rats, recorded in vitro
18 http://www.ncbi.nlm.nih.gov/pubmed/11600654 Evidence for plateau potentials in tail motoneurons of awake chronic spinal rats with spasticity
19 http://www.ncbi.nlm.nih.gov/pubmed/12764018 Neurobiological mechanisms involved in sleep bruxism
20 http://www.ncbi.nlm.nih.gov/pubmed/12580870 Case Report: severe amphetamine-induced bruxism: treatment with botulinum toxin
21 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602940/ Constitutively-active 5HT2/α1 receptors facilitate muscle spasms after human spinal cord injury

Oddly, I only seem to experience bruxism in response to trimonoamine releasers, not classical stimulants or selective SRAs.

ebola

How about SNRI's? Have you tried any?

 

[serotonin2A]

You are not going to find this information by searching for articles about "trigeminal and bruxism". Many investigations of motoneuron physiology are not directed toward a specific behavior (although there are exceptions) because the neurons have multiple functions. Plus, a lot of electrophysiology work is done in vitro, so the work is done in slices and the neurons are no longer connected to the muscles. So most of the time, you have to extrapolate what the functional implications of the in vitro findings would be. But if you do a Pubmed search for "5-HT2 motoneuron" you should find some of the studies.

 

[paranoid android]

I never got any jaw clenching from LSD, Psilocybin, MDMA/MDA or with any SNRI type tricyclics such as Amitriptyline or Trimipramine which is a strong NRI. I don't even get it from Bupropion which is notorious for causing it.

However cocaine and Amphetamines do give me jaw clenching plus i occasionally wake up with it for some reason.

 

[ebola?]

Never tried an SNRI before...and I don't plan on it.

ebola

 

[endotropic]

Motoneurons in the facial and trigeminal nuclei (as well as other cranial nerve nuclei) contain large numbers of 5-HT2A receptors, and activation of the receptors depolarizes the neurons and increases their excitability. This is one of the things that causes bruxism. Look up some of George Aghajanian's studies, although several other groups have studied how serotonin influences motorneuron membrane properties and firing, including spinal motoneurons. Dopamine and norepinephrine may also play a role in the response to MDMA but direct and indirect 5-HT2A receptor activation is the primary mechanism.

(about the earlier post about the basal ganglia and bruxism) The basal ganglia is involved in habits, among other things. So the direct and indirect pathways come into play with bruxism where someone is habitually grinding their teeth and cannot stop. But it is much more likely that MDMA is acting at the level of motoneurons to induce bruxism.

I never got any jaw clenching from LSD, Psilocybin, MDMA/MDA or with any SNRI type tricyclics such as Amitriptyline or Trimipramine which is a strong NRI. I don't even get it from Bupropion which is notorious for causing it.

However cocaine and Amphetamines do give me jaw clenching plus i occasionally wake up with it for some reason.

I don't think anyone gets bruxism from LSD, Psilocybin, or the many other 5-HT2A agonist psychedelics, which calls into question 5-HT2A agonism as a primary mechanism for monoamine releasing agent induced bruxism. Not that I have a better explanation, but the 5-HT2A theory doesn't mesh with the experiences of psychedelic users.

 

[serotonin2A]

I don't think anyone gets bruxism from LSD, Psilocybin, or the many other 5-HT2A agonist psychedelics, which calls into question 5-HT2A agonism as a primary mechanism for monoamine releasing agent induced bruxism. Not that I have a better explanation, but the 5-HT2A theory doesn't mesh with the experiences of psychedelic users.

It seems to be a functional selectivity issue. LSD and psilocin do not completely reproduce the effect of serotonin even though they act at 5-HT2A. It is also possible that serotonin is activating other receptors besides 5-HT2A that contribute to the response. But there is substantial evidence that 5-HT can activate signaling cascades coupled to 5-HT2A that hallucinogens are not capable of recruiting. This is one of the reasons why manipulations that increase 5-HT2A activation by serotonin do not cause hallucinogenic effects.

Look up some of the work by Schmid and Bohn for some background, although their work isn't specifically about motoneurons.

 

[crOOk]

It seems to be a functional selectivity issue. LSD and psilocin do not completely reproduce the effect of serotonin even though they act at 5-HT2A. [...] But there is substantial evidence that 5-HT can activate signaling cascades coupled to 5-HT2A that hallucinogens are not capable of recruiting. This is one of the reasons why manipulations that increase 5-HT2A activation by serotonin do not cause hallucinogenic effects.

Without a doubt.

It is also possible that serotonin is activating other receptors besides 5-HT2A that contribute to the response.

It's not just possible, there definitely are other receptors than the 5HT2Ar that serotonin can activate. Where did you get the idea that the 5HT2Ar alone is responsible for the cation influx? I have not seen this stated anywhere other than your posts. Are you saying there are no other 5HTr's on the motoneurons in question? Can bruxism be treated with 5HT2A antagonists? Please elaborate, I don't see where that claim is coming from.

Look up some of the work by Schmid and Bohn for some background, although their work isn't specifically about motoneurons.

Statements like these are very vague and they don't really help us in understanding the pathophysiology of bruxism. Could you please back them up with sources other than the names of two physiologists? If you are not willing to do so, there's really not much use in joining this discussion. I do think you could contribute a lot here, but not like this.

You sound like you have a very good idea of the pathomechanism involved in awake bruxism, but you should be well aware that there is no way your understanding is nearly as good as you make it out to be. While there are many clues, the issue is still a matter of ongoing debate. It also isn't possible to blame the symptom on a single receptor if you ask me. It's rarely that simple. Especially after I've gone through the effort to format and post an article which came to the conclusion that other monoamines (well, norepinephrine) are involved.

We have two options here: We either try to work together and go into the subject in detail or we leave it at what we know which is not much past what drugs can cause bruxism. Arguing about what protein is to blame without even listing sources is as unproductive as it gets.


EDIT: Btw are you German serotonin2? I noticed you are calling motor neurons motoneurons like I am, which afaik is only done on German.

 

[serotonin2A]

My last post was specifically about 5-HT2A and the question that was raised to it above. The Schmid and Bohm citation was included in that context, and is about 5-HT2A functional selectivity. If you can't be bothered to look it up in PubMed then that is fine, but I don't have time to do the searches for you. But anyone who searches for those authors would immediately locate their papers from 2008 and 2010 (if my memory is correct for the dates).

I am not German but the correct anatomical term for the cells is motoneurons and that is frequently what they are called in scientific studies.

If you are only interested in studies that are specifically about bruxism then you are not going to find very much, because that is not the context in which the trigeminal motor nuclei are usually studied. So you are going to have to read up on monoamines and trigeminal physiology and then try to understand if what is currently known makes sense in the context of bruxism.

I'm not trying to say 5-HT2A is the only receptor involved but that is the receptor for which involvement is most clear.

A good place to start looking for info about what mediates bruxism with MDMA is to see if anyone has been able to block it pharmacologically. I'm not sure if anyone has measured bruxism specifically in that context, but a few groups have given ketanserin, SSRIs, SNRIs, etc to people before they took MDMA.

 

[crOOk]

If you are only interested in studies that are specifically about bruxism then you are not going to find very much

Dude you've been too lazy to even read other peoples' posts. There are thousands of articles on bruxism and dozens (hundreds?) of reviews, as I have stated before. Not sure how you get the idea there aren't any out there, but you have apparently read none of them despite presenting yourself as an authority in the field.

No idea why, but I thought they were called motor neurons in English. My bad. We use motoneuron exclusively on German which explains my confusion.

Calling me lazy is ridiculous though. I took 30 minutes to format the above scitation. You are the lazy one here throwing around author names without contributing jackshit to the issue at hand. No offense.

 

[Leegrow]

I think most certainly jaw clenching is caused by serotonin release. I get mild and an almost silly ticklish jaw clenching on many drugs such as most opiates, benzos, psychs, dissociatives, etc. Which leads me to believe that typically the jaw clenching phenomena is caused by the release of serotonin.

 

[serotonin2A]

Dude you've been too lazy to even read other peoples' posts. There are thousands of articles on bruxism and dozens (hundreds?) of reviews, as I have stated before. Not sure how you get the idea there aren't any out there, but you have apparently read none of them despite presenting yourself as an authority in the field.

No idea why, but I thought they were called motor neurons in English. My bad. We use motoneuron exclusively on German which explains my confusion.

Calling me lazy is ridiculous though. I took 30 minutes to format the above scitation. You are the lazy one here throwing around author names without contributing jackshit to the issue at hand. No offense.

I'm not really sure why you were upset. The information I posted above was in response to what someone else wrote. I wasn't trying to contribute anything to the discussion other than to answer a question that was directed to me. If you don't feel like pasting the names into pubmed then you don't have to.

They certainly can be called motor neurons, it is a matter of personal preference. It's like the central nucleus of the amygdala versus the central amygdaloid nucleus.

I'm not presenting myself as an authority in the field, it's just that I am familiar with a lot of this literature. If I'm not taking the time to paste citations in it's because I'm not trying to research the topic. There is a bigger picture here than just bruxism and I think exposure to that aspect of the topic will make it easier to understand what is going on. One function of monoamines, in particular serotonin, it to control neuronal activity globally across the sleep wake cycle. It makes sense--there has to be a way to tell neurons that it is time to sleep or that they should be more active. One thing that serotonin does to facilitate that process is to increase the excitability of motoneurons. So if you only read about serotonin and the trigeminal nerve, you are potentially missing a lot of papers that are relevant to the topic. The trigeminal nucleus is only one place where serotonin excites motoneurons. If you inject rats with DOI they show very visible contractions of the muscles of the back that are due to 5-HT2A activation (PMID 1832068 ), which as caused by excitation of spinal motoneurons.
There is also a large literature about 5-HT and hallucinogen effects on motoneurons in the facial nucleus (PMID 156574, 7392793). Then there are effects on hypoglossal motoneurons that control breathing (14555716). I didn't have time to look up the trigeminal etc but you probably get the point. There are many more publications on those interactions if you do a search.

 

[crOOk]

I'm not really sure why you were upset. The information I posted above was in response to what someone else wrote. I wasn't trying to contribute anything to the discussion other than to answer a question that was directed to me. If you don't feel like pasting the names into pubmed then you don't have to.

I'm sorry, my tone was way off there. I did actually enter the names, but the information was far too unspecific to be applied to awake bruxism. Sure it does allow for speculation, but you know as well as I do that this isn't sufficient to close the case. It seemed to me that you are oversimplifying things which is inappropriate here since the case is far from being closed. You'd be the only one it is that simple to. Have you looked into the scitation I posted?

They certainly can be called motor neurons, it is a matter of personal preference. It's like the central nucleus of the amygdala versus the central amygdaloid nucleus.

German medical terminology is very different from the English, e.g. we use latin names for all anatomical structures. 'Central amygdaloid nucleus' becomes 'Nucleus Amygdalae Centralis'. Without ever paying any real attention to it I had noticed motor neurons is a relatively common expression in English and didn't realize the term motoneuron is actually just as common as it is in German. Enough of this though. :D

There is a bigger picture here than just bruxism and I think exposure to that aspect of the topic will make it easier to understand what is going on. One function of monoamines, in particular serotonin, it to control neuronal activity globally across the sleep wake cycle. It makes sense--there has to be a way to tell neurons that it is time to sleep or that they should be more active. One thing that serotonin does to facilitate that process is to increase the excitability of motoneurons. So if you only read about serotonin and the trigeminal nerve, you are potentially missing a lot of papers that are relevant to the topic. The trigeminal nucleus is only one place where serotonin excites motoneurons. If you inject rats with DOI they show very visible contractions of the muscles of the back that are due to 5-HT2A activation (PMID 1832068 ), which as caused by excitation of spinal motoneurons.
There is also a large literature about 5-HT and hallucinogen effects on motoneurons in the facial nucleus (PMID 156574, 7392793). Then there are effects on hypoglossal motoneurons that control breathing (14555716). I didn't have time to look up the trigeminal etc but you probably get the point. There are many more publications on those interactions if you do a search.

Yes I am aware of this and you do have a good point there. I did mention the role of raphe nuclei (which supply the enter brain with serotonin) play in micro arousals which come with increased serotonergic/noradrenergic activity I think using terms like monoaminergic drive is slightly misleading since that would include neurotransmitters like dopamine, histamine (both of which don't control cation influx, but dock to G protein coupled receptors), adrenaline or even dmt. :D Eventhough it might be obvious which monoamines are referred to with the expression to physiologists, it's a little misleading in this thread.

However, even with knowing the role of serotonin in microarousals and (which seem to cause sleep bruxism) mediating PIC, it is not entirely clear if that is the primary mechanism in awake bruxism as well. There is a lot of debate on this which is why I didn't like to see the issue oversimplified. That can be done when talking about related subjects, but not when awake bruxism is in the center of attention. It's just not that simple eventhough it looks like serotoninergic drive seems to play a very large role. MDMA use causing such massive bruxism is another strong indicator of this. On the other hand, it doesn't really explain why dopaminergic drugs drugs like l-dopa can also cause bruxism without exerting any (direct) influence on serotonergic or noradrenergic receptors. It has been proposed that it is in fact dopamine and it's effect on the basal ganglia is in fact an important cause of bruxism and serotonin activity being upstream of this mechanism, since it is not just acting directly onto the trigeminal nerve, but also mediating dopamine release. You can find an example of this in the first article I posted.

Just saying, the case is not clear yet. Thanks for the pubmed id's btw. I do research a shitload before posting any daring statements, so trust me I am anything but lazy (in this respect lol). It's just difficult discussing something like this without being able to quickly check every statement someone else makes. Sure I could just search for articles myself by author, it's just that it's conventional to mention the articles courselves to make life easier for readers. You know that as well as I do. Again, please excuse my tone earlier, it was way off.

 

[serotonin2A]

However, even with knowing the role of serotonin in microarousals

Unfortunately, I just don't think that we are going to learn much that is relevant to the original question by studying non-drug-induced bruxism. The response to MDMA has no non-drug counterpart. I don't think it is possible that spontaneous bruxism coud ever occur through the same mechanism as MDMA-induced bruxism because the serotonin system is so heavily regulated. The most relevant condition would probably be SSRI-induced bruxism. The fact that bruxism is a side-effect of SSRIs suggests that we are on the right track by linking serotonin to MDMA-induced bruxism.

This question was addressed in a 1996 review pubished in Progress in Neurobiology http://www.sciencedirect.com/science/article/pii/0301008296000275. I'll quote the relevant text in case you don't have access:

"In addition to euphoric properties, MDMA is a sympathetic nervous system stimulant which also stimulates somatic motor tone. Following ingestion of MDMA, human subjects experience jaw clenching, increased deep tendon reflexes and gait instability as well as increased heart rate and blood pressure (Steele et al., 1994). It is likely that both the vasomotor and the somatomotor effects of MDMA also are mediated by increases in extracellular levels of monoamines. Our laboratory recently examined the effect of microiontophoretic application of MDMA on glutamate-evoked firing of motoneurons in the hypoglossal nucleus of anesthetized rats. MDMA produced a slowly developing, long-lasting increase in glutamate-evoked firing of the motoneurons that was preceded in some cells by short-lasting inhibition (Figure. 12), effects that are mimicked by 5HT or NE application to facial or spinal motoneurons (McCall and Aghajanian, 1979; White and Neuman, 1980). The excitatory effect of MDMA was inhibited markedly by the non-specific 5HT antagonist methysergide (MTSG) and by the selective 5HT_2A,2C receptor antagonist ketanserin (KET). Both MTSG and KET (to a greater extent) partially inhibited glutamate-evoked firing when applied alone (perhaps by blocking the excitatory effects of tonically released 5HT) and increased the initial inhibitory effects of MDMA (Fig. 12). This 5HT antagonist-induced inhibition of the excitation produced by MDMA and “unmasking” of the inhibition produced by MDMA mimicked the effects that these antagonists have on 5HT-mediated excitation and inhibition of glutamate-evoked firing of spinal motoneurons (Jackson and White, 1990), suggesting that the MDMA effects were mediated in part by increasing extracellular levels of 5HT. Effects of MDMA (30 nA, 120 sec) on 22 hypoglossal motoneurons are shown in Fig. 13. MDMA produced a short-lasting but statistically significant inhibition of glutamate-evoked firing that was followed by a statistically significant increase in firing that did not return to baseline until 5–10 min after MDMA ejection offset. It is well established that 5HT, NE and DA all have excitatory effects on motoneurons in the brainstem and the spinal cord..."

In case the methods they used are unclear, MDMA and other compounds were applied to cells through a technique known as iontophoresis. A solution of the drug is loaded into a glass pipette that ends in a narrow tapered tip. Applying a current to the pipette will cause the drug to be expelled from the tip. So you can move the tip very close to a single cell that you are recording from and then apply the drug around the cell, with the amount of drug applied being proportional to the current.

I don't remember if anyone has done a similar experiment with MDMA and trigeminal motoneurons (notice that is what the neurons are called in the review), but we can extrapolate the findings from hypoglossal neurons to trigeminal neurons. If the same effect happened in the trigeminal nucleus then you would expect to see increased jaw tension and facilitated contraction, which could be expressed as bruxism. Notice also that the effect of MDMA was blocked by ketanserin.

 

[serotonin2A]

I'm sorry, my tone was way off there. I did actually enter the names, but the information was far too unspecific to be applied to awake bruxism.

I didn't mean to suggest that the reference was relevant to bruxism. I was just trying to give an example of how 5-HT2A functional selectivity can occur. It wouldn't be possible to specifically show that functional selectivity is occuring in this case because no one has investigated that. But it is never correct to say that an effect cannot be mediated by 5-HT2A unless it can also be produced by LSD and psilocybin. In additional to the functional selectivity issue, LSD and psilocybin are partial agonists. Sorry to get off track, but I thought it was an important point to make, because I can see why it would seem weird that MDMA can produce effects via 5-HT2A that are not produced by other agonists.

German medical terminology is very different from the English, e.g. we use latin names for all anatomical structures. 'Central amygdaloid nucleus' becomes 'Nucleus Amygdalae Centralis'.

I'm sorry, I should have said that amygdaloid was Greek, not Latin. You'll find some papers that use "amygdaloid nucleus" and other that use "nucleus of the amygdala". The point I was trying to make is that neuroscientists use multiple anatomical terms for structures. It often depends on who trained them and what is the custom in their sub-field.

I usually write posts on my phone and it is almost impossible to copy and paste. And I am often listing studies from memory, so I'll know the authors and maybe the year but won't remember the exact citation.

 

[crOOk]

I didn't mean to suggest that the reference was relevant to bruxism. I was just trying to give an example of how 5-HT2A functional selectivity can occur. It wouldn't be possible to specifically show that functional selectivity is occuring in this case because no one has investigated that. But it is never correct to say that an effect cannot be mediated by 5-HT2A unless it can also be produced by LSD and psilocybin. In additional to the functional selectivity issue, LSD and psilocybin are partial agonists. Sorry to get off track, but I thought it was an important point to make, because I can see why it would seem weird that MDMA can produce effects via 5-HT2A that are not produced by other agonists.

Yeah absolutely, a very important point which is often overlooked on these boards. I was surprised endotropic didn't realize that at the time he made his posts. Pretty sure I've seen him explain this to someone in another thread. :D

I'm sorry, I should have said that amygdaloid was Greek, not Latin. You'll find some papers that use "amygdaloid nucleus" and other that use "nucleus of the amygdala". The point I was trying to make is that neuroscientists use multiple anatomical terms for structures. It often depends on who trained them and what is the custom in their sub-field.

Generally all anatomical expressions are Latin, while pathological processes have Greek names. The word amygdala exists in both Latin and Greek, with the Greek word being the one the Latin term is derived from. The term used when referring to the anatomical structure is the Latin one though, as one can see when looking at how it is declined (e.g. nom. pl. and gen. sg. amygdalae).

While I generally only read English literature and consider the English nomenclature far more convenient, I can't deny I don't value the fact that we still decline all the Latin (and to lesser extent Greek) terms correctly in Germany. Pretty sure we are alone with that though.

 

[Clos16]

I took my first dose of a dopamine supplement yesterday morning, i woke up at around 4 AM the next day with my jaw and teeth sore as hell.From that experience i am sure the dopamine was the cause, as its the only variable i implemented to my daily routine.

 

[aced126]

I have heard magnesium reverses MDMA-induced bruxism, and that magnesium is depleted causing involuntary jaw contractions. I'm not completely sure though as that information was from a harm reduction site, definitely not a purely scientific source.