Help Me With My Dissertation On Serotonin Guys?

[Combie]

Hello guys, been a while since ive been here, but ive been kinda busy with my education. Im doing a degree in herbal medicine, and am in my third year, which means dissertation.

Ive been trying (and failing) to convince everyone on my course that serotonin is not really something you want to promote, so ive decided to do my dissertation on St. Johns Wort, as this will give me an excuse to understand serotonin, and hopefully convert a few people (though ill not hold my breath there, lol). Im focussing on the mechanisms by which SJW relieves depression (which it does, but in a backward, dangerous, lame kind of way), and also how it simultaneously causes sexual dysfunction, primarily anorgasmia and loss of sensation.

Im calling my project "Why do you build me up, just to let me down?"

So, im wondering what juicy research papers you guys might have, or what info/help you might be able to give me in understanding this. I was thinking maybe i could set up a dropbox and make all my related pdfs available to all, if this is within forum rules?

muchos gracias

 

[goodandevil]

Hello guys, been a while since ive been here, but ive been kinda busy with my education. Im doing a degree in herbal medicine, and am in my third year, which means dissertation.

Ive been trying (and failing) to convince everyone on my course that serotonin is not really something you want to promote, so ive decided to do my dissertation on St. Johns Wort, as this will give me an excuse to understand serotonin, and hopefully convert a few people (though ill not hold my breath there, lol). Im focussing on the mechanisms by which SJW relieves depression (which it does, but in a backward, dangerous, lame kind of way), and also how it simultaneously causes sexual dysfunction, primarily anorgasmia and loss of sensation.

Im calling my project "Why do you build me up, just to let me down?"

So, im wondering what juicy research papers you guys might have, or what info/help you might be able to give me in understanding this. I was thinking maybe i could set up a dropbox and make all my related pdfs available to all, if this is within forum rules?

muchos gracias

Check out serotonin papers 9n raypeat.com, he has excellent references.

 

[answersfound]

Maybe talk about seroquel and robin Williams death. I think he was on it. Also, talk about LSD and its treatment of depression.

 

[thyrulian]

Funny, I was writing about serotonin for another forum and ended up digging up some very blatantly damning stuff.

Linking serotonin to diabetes should be quite the easy route, considering its general support of antiinsulinogenic counterregulatory hormones, angiotensin II, aldosterone, IL1beta, IL6, etc., all of which are easily implicated in the pathology of diabetes.

I'd also look to:

-gut-derived serotonin's effect on bone mass
-the fact that androgenic activity means greater SERT expression (seems testosterone can only increase serotonin through aromatase) to beneficial effect (for diabetes)
-whereas more estrogenic activity means less SERT expression to detrimental effect (also considering the importance of SHBG's regulation of estrogen in regard to diabetes)
-SSRIs' link to SIADH (syndrome of inappropriate antidiurectic hormone secretion)
-glutamate & serotonin's similar effect on glycolysis - a lot of serotonin's damage might be done through the glutamatergic 5-HT2A receptor, hinting at serotonin's not-so-calming nature
-its possible cholinergic mechanisms (5HT3R) that also suggest such
-its responsibility for the intensity of pain a venom delivers
-the ability of amantadine to aid glucose tolerance by reducing serotonin
-the conflicting actions of NSAIDs & SSRIs.

Here're some refies:

High-Dose Testosterone Treatment Increases Serotonin Transporter Binding in Transgender People

Improved oral glucose tolerance following antiserotonin treatment in patients with chemical diabetes. (wherein they implicate reduced secretion of counterregulatory hormones as plausibile mechanism)

Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men.

Adiponectin is beneficial: http://img.medscape.com/fullsize/migrat ... 6.fig1.gif

Serotonin antagonist increases it: http://care.diabetesjournals.org/content/26/8/2477.full

Exposure to high glutamate concentration activates aerobic glycolysis but inhibits ATP-linked respiration in cultured cortical astrocytes.

Serotonin-induced decrease in brain ATP, stimulation of brain anaerobic glycolysis and elevation of plasma hemoglobin; the protective action of calmodulin antagonists.

Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors

A pharmacological analysis of the mode of action of serotonin (5-hydroxytryptamine) upon the guinea-pig ileum

More recent studies indicate that the 5-HT3 receptor, which equates to Gaddum & Picarelli's (1957) ‘M’ receptor, most likely accounted for the responses. Both receptors stimulate the release of acetylcholine, although functional evidence indicates that 5-HT3 receptor-mediated contractions are also mediated, in part, by the concomitant release of Substance P (Buchheit et al., 1985). This contemporary knowledge may explain the differences in sensitivity of 5-HT to atropine reported in the early studies with this tissue, since the relative contributions of acetylcholine and Substance P to 5-HT-induced contractions probably varies considerably with animal strain, age and experimental conditions.

This quote says a lot:

The fact that glutamatergic axons innervate and excite the C1 (Ad) but not the A5 (NA) neurons (by acting at NMDA receptors) explains why amantadine (a NMDA antagonist) interferes with the adrenal but not with the neural sympathetic activity. With respect to this, experimental evidences obtained from our laboratory, demonstrated that a small dose of amantadine (administered without glucose) provokes absolute minimization of the adrenaline plasma concentration.24,29

In addition to all the above, some other factors should be considered in order to understand the ability by amantadine to annul the glucagon-induced excitatory effect at the CNS C1 (Ad) + peripheral adrenal sympathetic axis, which would explain its insulinogenic + hypoglycemic effects. For instance, the drug was able to provoke maximal reduction of both plasma serotonin and platelet serotonin concentration. This circulating indolamine exerts an inhibitory effect at the beta-cell level and in addition is able to excite alpha-cells, which secrete glucagon.37–41 Furthermore, plasma serotonin is able to excite the adrenal glands,39,42 directly. Thus, the reduction of plasma serotonin plus platelet serotonin circulating values registered in the present study should be taken into account in order to understand the hypoglycemic effect triggered by amantadine, when this drug was added to an oral glucose load.

...

In addition to the above, it has been shown that other drugs like tianeptine, which also minimizes plasma serotonin concentration is able to enhance plasma insulin secretion.10 This fact should be attributed to the direct inhibitory effect exerted by this indolamine at the beta-cell level.

Amantadine reduces glucagon and enhances insulin secretion throughout the oral glucose tolerance test: central plus peripheral nervous system mechanisms

 

[DaveFoster]

There are some great links on this page. I sincerely think that you're going to find yourself in a situation where you will not just be fighting against serotonin, but also against the agenda of academia and the Western world.

When you support a worldview that upholds the physiological preference for dopamine over serotonin, you inevitably will also be supporting testosterone, and when you do that, you will find that certain favorable outlooks will surface concerning various behavioral dispositions; those not upheld by the powers that be. I am, of course, referring to asserting one's own place in the world over mimicking the already-present structures of power and serving these bodies. In other words, self-expression and firm values will always be the enemy of supplication and compromise.

 

[aguilaroja]

post 113667 ... serotonin is not really something you want to promote, so ive decided to do my dissertation on St. Johns Wort,... Im focussing on the mechanisms by which SJW relieves depression...and also how it simultaneously causes sexual dysfunction, primarily anorgasmia and loss of sensation....

One thing to point out is that tianeptine, a serotonin ANTAGONIST, is comparably effective to major SSRI agents.

http://www.ncbi.nlm.nih.gov/pubmed/11463130
http://en.wikipedia.org/wiki/Tianeptine
"Tianeptine shows efficacy against serious depressive episodes (major depression), comparable to amitriptyline, imipramine and fluoxetine, but with significantly fewer side effects. It was shown to be more effective than maprotiline in a group of people with co-existing depression and anxiety.[2] Tianeptine also displays significant anxiolytic properties and is useful in treating a spectrum of anxiety disorders including panic disorder,"

Tianeptine, a serotonin inhibitor, also modulates the hypothalmic-pituitary-adrenal axis, which is disturbed in depressive states.
http://www.ncbi.nlm.nih.gov/pubmed/23994757
"When the antidepressant tianeptine was administered, HPA axis hyperactivity was attenuated and specific neuronal defects were ameliorated in both sexes."

Tianeptine may also relieve the over-activation of glutamate signaling in the brain.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902200/
"Tianeptine has been shown to inhibit the pathological stress-induced changes in glutamatergic neurotransmission in the hippocampus and amygdala in animal models"

St. John's Wort has many constituents. It has been widely hypothesized that its effect is mainly through its SSRI-like serotonin promoting action. But other aspects of SJW are studied.

http://www.ncbi.nlm.nih.gov/pubmed/7704987
"St. John's wort (Hypericum perforatum L., SJW) contains numerous compounds with documented biological activity. Constituents that have stimulated the most interest include the naphthodianthrones hypericin and pseudohypericin, a broad range of flavonoids, and the phloroglucinols hyperforin and adhyperforin."

For instance, SJW promotes intracellular sodium:
http://www.ncbi.nlm.nih.gov/pubmed/11277608
"Hypericum possesses a unique pharmacology in that it displays the pharmacology of many classes of antidepressants and new mechanisms not typical of standard antidepressants. The most potent of all its action is the moderate to high potency for inhibition of the reuptake of monoamines, serotonin, dopamine and noradrenaline and the amino-acid neurotransmitters GABA and glutamate. Unlike standard reuptake inhibitors, hypericum exerts this reuptake inhibition non-competitively by enhancing intracellular Na+ ion concentrations. At a receptor level, chronic treatment with hypericum downregulates beta1-adrenoceptor, upregulates post-synaptic 5-HT1A receptors and 5-HT2 receptors. Although the major constituent responsible for the antidepressant effect is thought to be hyperforin, other constituents such as hypericin, pseudohypericin, flavonoids and oligomeric procyanidines may also play a direct or indirect role. While reuptake inhibition may more than likely be responsible for most of the antidepressant effect, other mechanisms may also contribute alone or in combination to exert the overall antidepressant action."

And SJW may not be a potent Monoamine oxidase A (MAO-A) inhibitor:
https://www.ncbi.nlm.nih.gov/pubmed/21463543

SJW may be neuroprotective as an NMDA receptor-antagonist
http://www.ncbi.nlm.nih.gov/pubmed/16936454
"hyperforin has NMDA-receptor-antagonistic and potential neuroprotective effects in vitro. This effect may contribute to the therapeutic effectiveness of St. John's wort extracts in some situations, for example, for relapse prevention in alcoholism."

In regard to the anorgasmia effect (ouch!), it might be recalled the SJW inhibits some smooth muscle contraction:
http://www.ncbi.nlm.nih.gov/pubmed/15245964
"SJW inhibits excitatory transmission of the rat urinary bladder and also directly inhibits smooth muscle contractility. The inhibitory effect on excitatory transmission could involve, at least in part, opioid receptors."

 

[Combie]

Some great links, thanks! I'll plough through those on the train tomorrow. Awesome

 

[tara]

post 113667 Im calling my project "Why do you build me up, just to let me down?"

:)

 

[Lokzo]

Okay I have been experimenting with SJW in the last few months, and each time with different extracts. I would love to hear other people's experiences!