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Natural Serotonin Antagonists

natural serotonin serotonin antagonists blockers

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#1 Area-1255

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Posted 26 August 2014 - 05:51 PM


Shilajit is found to protect against serotonin induced cognitive deficits by rapidly depleting serotonin activity; especially in the Hippocampus. This is also a proposed mechanism by which Shilajit rejuvenates normal libido / sexual function.

Ginseng has effects in the hypothalamus, reducing serotonin activity there.

Vitex decreases serotonin rapidly, and Yohimbe acts as a competitive antagonist at multiple receptors.

 

I am also going to add a couple more to the article soon.

 

http://area1255.blog...ntagonists.html


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#2 markymark

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Posted 27 August 2014 - 06:18 AM

Interesting,

But how come the big price difference between Dragnon H High Mountain Shilajit 500 mg 60 cps (approx 30 USD) and, say, Swansons 60 cps 400 mg: 6,57 UK Pound?

 

 

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#3 Area-1255

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Posted 27 August 2014 - 12:29 PM

 

Interesting,

But how come the big price difference between Dragnon H High Mountain Shilajit 500 mg 60 cps (approx 30 USD) and, say, Swansons 60 cps 400 mg: 6,57 UK Pound?

 

 

 

Their's is high mountain and of the black variety I believe, just different concentrations of the active's ; fulvic,humilic acids etc


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#4 Area-1255

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Posted 03 September 2014 - 05:10 AM

 

Interesting,

But how come the big price difference between Dragnon H High Mountain Shilajit 500 mg 60 cps (approx 30 USD) and, say, Swansons 60 cps 400 mg: 6,57 UK Pound?

 

 

 

Also an effective synergist to help both balance serotonin out and aid in GABA would be Ashwagandha. I've noticed Shilajit + Ash gives strong focus and a sense of completeness. All of those would speed reaction time as well.


Edited by Area-1255, 03 September 2014 - 05:11 AM.

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#5 Area-1255

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Posted 26 September 2014 - 04:14 AM

Ken @ root of the matter has really good shilajit as well.


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#6 Area-1255

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Posted 30 November 2014 - 09:15 PM

Anyone else try shilajit?


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#7 forexworld12

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Posted 05 January 2015 - 09:51 AM

Anyone else try shilajit?

Tried for a day or two made me agitated/restless 

how many mg should one take to effectively reduce serotonin 500 mg ? 1000 mg ? 2000 mg ?



#8 Area-1255

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Posted 05 January 2015 - 04:29 PM

 

Anyone else try shilajit?

Tried for a day or two made me agitated/restless 

how many mg should one take to effectively reduce serotonin 500 mg ? 1000 mg ? 2000 mg ?

 

At least 1000 mg.


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#9 forexworld12

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Posted 27 March 2015 - 10:51 AM

I was just reading about it and the reports say it increases dopamine and reduces serotonin in the prefrontal cortex and other brain region - it was not mentioned ..

 

1) is there any specific study that shows it decreases serotonin in the hipocampus and other brain region ? 

 

Also 2000mg significantly increases dopamine and reduces serotonin in the pre frontal cortex 

 

http://www.sabinsa.c...t/shilajit.pdf 

 

2) In theory shouldn't it work better than agomelatine ? it does the same thing without requiring to attach to the 5ht2c ? I am on day 3 and seems no effect on mood.. 


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#10 niner

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Posted 27 March 2015 - 11:59 AM

If the point of antidepressants is increasing serotonin levels, why does shilajit not mess with your mood, if it's reducing serotonin?


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#11 Strelok

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Posted 27 March 2015 - 04:37 PM

Generally speaking, would a serotonin antagonist upregulate serotonin receptors over time?


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#12 Area-1255

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Posted 27 March 2015 - 09:44 PM

If the point of antidepressants is increasing serotonin levels, why does shilajit not mess with your mood, if it's reducing serotonin?

Serotonin is involved in a complex orchestration of neural networks and signaling modulation...there's a delicate balance that precedes it's (serotonin) determining of glutamate and  GABA functioning - and that is receptor and transporter concentration. 
 
Anyone who has experienced it can tell you SSRI's can cause anhedonia; which makes sense as serotonin inhibits dopamine and many other pleasure hormones as it's levels become elevated quickly or chronically.
 
The benefits of SSRI's are paradoxically, not only to do with their effects on serotonin - what was once known about them has been expanded, the latest expansive research shows that (or perhaps reiterates) many of them need to be re-evaluated because their effects may not be totally due to serotonergic changes but rather, neurosteroid binding and frontal cortex modifications as well as secondary epi-genetic changes.

 

 

http://www.psychiatrictimes.com/articles/neurosteroids-and-psychiatric-disorders/page/0/2/

 


 

 

 

Med Sci Monit.[/size] 2003 Nov;9(11):RA270-5.[/size]
The role of neurosteroids in the anxiolytic,antidepressive- and anticonvulsive effects of selective serotonin reuptake inhibitors.
Członkowska AI1Zienowicz MBidziński AMaciejak PLehner MTaracha EWisłowska APłaźnik A.
Author information
 

Abstract

The introduction of SSRIs to the clinic was a turning point in the treatment of depression and related mental disorders. Nowadays, it is becoming more and more evident that SSRIs are equally effective in anxiety states and some types of epilepsy. However, the mechanism of their central action is not fully understood. They not only block the serotonin transporter, but also bind to different types of monoaminergic receptors (serotonergic, dopaminergic) and interact with the synthesis of neurosteroids, in this way modifying the excitability of the central nervous system. The aim of this review is to update information on the preclinical and clinical effects of SSRI, with special emphasis put on the probable role of neurosteroids and the GABAA receptor complex in the mechanism of their action.



PMID:   14586292   [PubMed - indexed for MEDLINE]

Eur Neuropsychopharmacol.[/size] 2003 Oct;13(5):327-32.[/size]
Brain neurosteroid changes after paroxetine administration in mice.
Nechmad A1Maayan RSpivak BRamadan EPoyurovsky MWeizman A.
Author information
 

Abstract

Although it is known that selective serotonin reuptake inhibitors (SSRIs), as other antidepressants, elevate mood only after 3-4 weeks of treatment, the mechanism responsible for this delay is not understood. SSRIs have been demonstrated to alter the levels of neurosteroids such as allopregnanolone (THP) which possess anxiolytic and mood-elevating properties. We compared the effect of 9 and 21 days i.p. administration of paroxetine, a potent SSRI, on the synthesis of THP and its precursor, 5alpha-dihydroprogesterone (DHP), in the mouse cortex, hypothalamus and olfactory bulb. Cortex, olfactory bulb and hypothalamus synthesized levels of DHP were significantly raised after 9 days of paroxetine administration, whereas a significant rise in the THP synthesized level was observed only after 21 days of treatment. Peripheral synthesis of DHP, measured by the level in serum, significantly increased after 9 days, but reverted to normal values after 21 days. No increase was detected in serum THP levels either after 9 or 21 days treatment. Differences in peripheral and brain synthesis indicates independence in brain synthesis. The data indicate that paroxetine administration differentially increases [3H]DHP and [3H]THP content, depending on the duration of the treatment. Our results suggest that brain THP may be involved in the antidepressive and anxiolytic activity of paroxetine.



PMID:   12957330   [PubMed - indexed for MEDLINE]

Psychopharmacology (Berl).[/size] 2003 Jan;165(2):97-110. Epub 2002 Nov 6.[/size]
Neurosteroids in depression: a review.
van Broekhoven F1Verkes RJ.
Author information
 

Abstract
RATIONALE:
A deregulation in concentrations of the neurosteroids (allo)pregnanolone and 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-TH DOC) has been found in depressed patients. These levels normalize following treatment with selective serotonin reuptake inhibitors (SSRIs). Furthermore, administration of the neurosteroid dehydroepiandrosterone (DHEA) to depressed patients is associated with an improvement in the symptoms of depression.
OBJECTIVE:
The aim of the present review is to clarify the mechanisms whereby neurosteroids, particularly allopregnanolone and DHEA, are involved in depression and to discuss the effect of SSRIs on allopregnanolone concentration.
METHODS:
Literature on preclinical and clinical research has been analyzed in relation to the pathophysiology of depression.
RESULTS:
Decreased plasma and cerebrospinal fluid concentrations of allopregnanolone in depressed patients increase to normal levels following effective psychopharmacological treatment. This might either be a physiological aspect of improvement in the symptoms of depression or a pharmacologically induced alteration. Several findings support the hypothesis of an antidepressant effect of allopregnanolone. These include an antidepressant effect demonstrated in an animal model of depression and a suppressing effect on corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) gene expression. SSRIs increase levels of allopregnanolone, but this effect is not confined to this class of drugs alone. The beneficial effect of DHEA administration in depressed patients might result from its sigma 1 receptor-mediated enhancement of noradrenaline and serotonin neurotransmission, antiglucocorticoid effects, and cognition enhancing effects.
CONCLUSIONS:
Indirect genomic (allopregnanolone) and non-genomic (allopregnanolone and DHEA) mechanisms are involved in the neurosteroidogenic pathophysiology of depression. Clinical studies in homogeneous groups of non-pharmacologically treated depressed patients are required to elucidate this relationship further.



PMID:   12420152   [PubMed - indexed for MEDLINE]

Med Sci Monit.[/size] 2003 Nov;9(11):RA270-5.[/size]
The role of neurosteroids in the anxiolytic,antidepressive- and anticonvulsive effects of selective serotonin reuptake inhibitors.
Członkowska AI1Zienowicz MBidziński AMaciejak PLehner MTaracha EWisłowska APłaźnik A.
Author information
 

Abstract

The introduction of SSRIs to the clinic was a turning point in the treatment of depression and related mental disorders. Nowadays, it is becoming more and more evident that SSRIs are equally effective in anxiety states and some types of epilepsy. However, the mechanism of their central action is not fully understood. They not only block the serotonin transporter, but also bind to different types of monoaminergic receptors (serotonergic, dopaminergic) and interact with the synthesis of neurosteroids, in this way modifying the excitability of the central nervous system. The aim of this review is to update information on the preclinical and clinical effects of SSRI, with special emphasis put on the probable role of neurosteroids and the GABAA receptor complex in the mechanism of their action.



PMID:   14586292   [PubMed - indexed for MEDLINE]

Proc Natl Acad Sci U S A.[/size] 1999 Nov 9;96(23):13512-7.[/size]
Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes.
Griffin LD1Mellon SH.
Author information
 

Abstract

The neurosteroid 3alpha-hydroxysteroid-5alpha-pregnan-20-one (allopregnanolone) acts as a positive allosteric modulator of gamma-aminobutyric acid at gamma-aminobutyric acid type A receptors and hence is a powerful anxiolytic, anticonvulsant, and anesthetic agent. Allopregnanolone is synthesized from progesterone by reduction to 5alpha-dihydroprogesterone, mediated by 5alpha-reductase, and by reduction to allopregnanolone, mediated by 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD). Previous reports suggested that some selective serotonin reuptake inhibitors (SSRIs) could alter concentrations of allopregnanolone in human cerebral spinal fluid and in rat brain sections. We determined whether SSRIs directly altered the activities of either 5alpha-reductase or 3alpha-HSD, using an in vitro system containing purified recombinant proteins. Although rats appear to express a single 3alpha-HSD isoform, the human brain contains several isoforms of this enzyme, including a new isoform we cloned from human fetal brains. Our results indicate that the SSRIs fluoxetine, sertraline, and paroxetine decrease the K(m) of the conversion of 5alpha-dihydroprogesterone to allopregnanolone by human 3alpha-HSD type III 10- to 30-fold. Only sertraline inhibited the reverse oxidative reaction. SSRIs also affected conversions of androgens to 3alpha- and 3alpha, 17beta-reduced or -oxidized androgens mediated by 3alpha-HSD type II(Brain). Another antidepressant, imipramine, was without any effect on allopregnanolone or androstanediol production. The region-specific expression of 3alpha-HSD type II(Brain) and 3alpha-HSD type III mRNAs suggest that SSRIs will affect neurosteroid production in a region-specific manner. Our results may thus help explain the rapid alleviation of the anxiety and dysphoria associated with late luteal phase dysphoria disorder and major unipolar depression by these SSRIs.



PMID:   10557352   [PubMed - indexed for MEDLINE]    PMCID:   PMC23979     Free PMC Article


Edited by Area-1255, 27 March 2015 - 09:49 PM.

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#13 Area-1255

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Posted 27 March 2015 - 09:52 PM

Generally speaking, would a serotonin antagonist upregulate serotonin receptors over time?

Depends, but in most cases - especially dealing with 5-HT2A/2C receptors - if you stimulate or block them excessively; they downregulate..there's a huge contrast between what happens in the serotonergic family as opposed to dopamine, acetylcholine,  sigmaR's etc

 

Serotonin receptors seem to become de-sensitized quicker than a lot of other types of receptors, and there's a much less significant and much shorter lag in serotonin downregulation > dopamine receptor downregulation...that means it would take roughly twice or more than the amount of time to downregulate dopamine than serotonin.

 

5-HT1A and the type 2 family seems to be most prone to de-sensitization, and downregulation, respectively.


Edited by Area-1255, 27 March 2015 - 09:55 PM.

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#14 GoingPrimal

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Posted 01 April 2015 - 03:50 PM

I've tried shilajit on many occasions, and still use low doses today in one of my herbal mixes. Other than some increased libido I can't say I noticed much, even though I was hyped after hearing all of its benefits.

 

Anyone tried Lotus Blooming Herbs' "Authentic Shilajit"? I've read that traditionally authentic shilajit is a paste, and supposedly can't be made into a powder, though I can't provide any sources for that. Makes me wonder if I've been being jipped this whole time.



#15 the_apollo

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Posted 02 April 2015 - 12:25 AM

 

Serotonin is involved in a complex orchestration of neural networks and signaling modulation...there's a delicate balance that precedes it's (serotonin) determining of glutamate and  GABA functioning - and that is receptor and transporter concentration. 
 
Anyone who has experienced it can tell you SSRI's can cause anhedonia; which makes sense as serotonin inhibits dopamine and many other pleasure hormones as it's levels become elevated quickly or chronically.

 

 

A study detailing serotonin reuptake inhibitors points to the activation of 5HT2C in the VTA as being responsible, as the application of an 5HT2C receptor antagonist reverse the decrease in dopamine caused by an SSRI (in this case Escitalopram).

http://www.ncbi.nlm....les/PMC2674976/


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#16 airplanepeanuts

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Posted 03 April 2015 - 06:52 PM

If the point of antidepressants is increasing serotonin levels, why does shilajit not mess with your mood, if it's reducing serotonin?

I think Galaxyshok mentioned on this forum that shilajit unbalances his mood. 



#17 Area-1255

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Posted 03 April 2015 - 07:32 PM

 

 

Serotonin is involved in a complex orchestration of neural networks and signaling modulation...there's a delicate balance that precedes it's (serotonin) determining of glutamate and  GABA functioning - and that is receptor and transporter concentration. 
 
Anyone who has experienced it can tell you SSRI's can cause anhedonia; which makes sense as serotonin inhibits dopamine and many other pleasure hormones as it's levels become elevated quickly or chronically.

 

 

A study detailing serotonin reuptake inhibitors points to the activation of 5HT2C in the VTA as being responsible, as the application of an 5HT2C receptor antagonist reverse the decrease in dopamine caused by an SSRI (in this case Escitalopram).

http://www.ncbi.nlm....les/PMC2674976/

 

Everything is a certain balance. Yet almost every serotonin receptor has either.

 

1.) Negative effect on Testosterone or other hormones. Including neurosteroids that have anxiolytic properties.

2.) Negative effects on dopamine and other neurotransmitters. 

 

Most of all serotonin receptors will increase cortisol, ACTH etc...and in many cases , this causes adrenaline rush/issues which means serotonin just makes you more irritable, if not irritable then you will be NUMBED OUT, and have almost ZERO emotional capacity....this seems to come from excess HPTA inhibition and / or adrenal burnout from serotonin constantly releasing cortisol and dynorphins...beta-endorphin has positive effects under CERTAIN CIRCUMSTANCES, but having HIGH resting levels of b-endorphin encourages people to be lazy and watch TV all day. (example)


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#18 Strelok

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Posted 03 April 2015 - 10:07 PM

 

 

 

Serotonin is involved in a complex orchestration of neural networks and signaling modulation...there's a delicate balance that precedes it's (serotonin) determining of glutamate and  GABA functioning - and that is receptor and transporter concentration. 
 
Anyone who has experienced it can tell you SSRI's can cause anhedonia; which makes sense as serotonin inhibits dopamine and many other pleasure hormones as it's levels become elevated quickly or chronically.

 

 

A study detailing serotonin reuptake inhibitors points to the activation of 5HT2C in the VTA as being responsible, as the application of an 5HT2C receptor antagonist reverse the decrease in dopamine caused by an SSRI (in this case Escitalopram).

http://www.ncbi.nlm....les/PMC2674976/

 

Everything is a certain balance. Yet almost every serotonin receptor has either.

 

1.) Negative effect on Testosterone or other hormones. Including neurosteroids that have anxiolytic properties.

2.) Negative effects on dopamine and other neurotransmitters. 

 

Most of all serotonin receptors will increase cortisol, ACTH etc...and in many cases , this causes adrenaline rush/issues which means serotonin just makes you more irritable, if not irritable then you will be NUMBED OUT, and have almost ZERO emotional capacity....this seems to come from excess HPTA inhibition and / or adrenal burnout from serotonin constantly releasing cortisol and dynorphins...beta-endorphin has positive effects under CERTAIN CIRCUMSTANCES, but having HIGH resting levels of b-endorphin encourages people to be lazy and watch TV all day. (example)

 

 

So would it be a terrible idea to take a modest dose of trazodone for insomnia?

 


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#19 Area-1255

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Posted 03 April 2015 - 11:35 PM

 

 

 

 

Serotonin is involved in a complex orchestration of neural networks and signaling modulation...there's a delicate balance that precedes it's (serotonin) determining of glutamate and  GABA functioning - and that is receptor and transporter concentration. 
 
Anyone who has experienced it can tell you SSRI's can cause anhedonia; which makes sense as serotonin inhibits dopamine and many other pleasure hormones as it's levels become elevated quickly or chronically.

 

 

A study detailing serotonin reuptake inhibitors points to the activation of 5HT2C in the VTA as being responsible, as the application of an 5HT2C receptor antagonist reverse the decrease in dopamine caused by an SSRI (in this case Escitalopram).

http://www.ncbi.nlm....les/PMC2674976/

 

Everything is a certain balance. Yet almost every serotonin receptor has either.

 

1.) Negative effect on Testosterone or other hormones. Including neurosteroids that have anxiolytic properties.

2.) Negative effects on dopamine and other neurotransmitters. 

 

Most of all serotonin receptors will increase cortisol, ACTH etc...and in many cases , this causes adrenaline rush/issues which means serotonin just makes you more irritable, if not irritable then you will be NUMBED OUT, and have almost ZERO emotional capacity....this seems to come from excess HPTA inhibition and / or adrenal burnout from serotonin constantly releasing cortisol and dynorphins...beta-endorphin has positive effects under CERTAIN CIRCUMSTANCES, but having HIGH resting levels of b-endorphin encourages people to be lazy and watch TV all day. (example)

 

 

So would it be a terrible idea to take a modest dose of trazodone for insomnia?

 

 

Trazodone isn't strictly an SSRI - it's also a strong alpha-1-blocker, which is the main reason why it has a sedative effect. Most anti-psychotics also potently block alpha-1-adrenergic receptors - which is again, the main reason for their sedative effects. The antihistamine effect amplifies the adrenergic blockade effects...

 

Trazodone has part of that property...

 

Serotonin really doesn't alleviate insomnia...in fact, it can cause it...the only time serotonin has a specific anti-insomnia effect is when it converts into melatonin.

 

Melatonin comes from serotonin via the enzymes  serotonin-N-acetyltransferase    &  and HIOMT (hydroxyindole-O-methyltrasferase)...

Biological Synthesis and Metabolism of Melatonin

 

 

With that being said, serotonin does have anxiolytic / calming properties via 5-HT1A autoreceptors - the reasons are more complicated than most think. Autoreceptors reduce the activity of a neurotransmitter, therefore serotonin 1A inhibits itself, therefore producing a decrease in serotonergic excitation at other receptors. 

 

So it's actually the DECREASE in serotonin via autoreceptor activation that produces less anxiety....

 

Also 5-HT1A is negatively coupled to adenylate cyclase and it has diverse effects on neuropeptides, the other anxiolytic effect probably has to do with 5-HT1A being present on oxytocinergic neurons. 

 

Therefore 5-HT1A receptor activation is just about the only serotonin receptor that alleviates anxiety. It does so by.

 

  • Reducing serotonin at other receptors.
  • Increasing oxytocin release.

 

 

HOWEVER, these receptors can easily become de-sensitized if you stimulate them too much, leading to nullification of this effect and thus lack of anxiolytic effect from serotonin....this is one of the hypothesis of violent criminals, they no longer respond to the autoreceptors of serotonin thus there are no brakes and serotonin is flooding the brain leading to erratic behavior. 

 

 

 

Eur Neuropsychopharmacol. 2001 Feb;11(1):15-24.

Rapid desensitization of 5-HT(1A) receptors in Fawn-Hooded rats after chronic fluoxetine treatment.
Abstract

Anxiety, platelet serotonin (5-HT) content and functions of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were measured in Sprague--Dawley (SD) and Fawn-Hooded (FH) rats, a strain with genetically impaired 5-HT storage and reuptake system and a putative model of depression and anxiety. In addition, the effects of 7 and 16 days treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine on 8-OH-DPAT-induced responses were studied. FH rats showed significantly higher anxiety in the social interaction test, and much lower platelet 5-HT content compared to SD rats. The efficacy of 8-OH-DPAT (15-120 microg/kg, i.v.) to induce lower lip retraction (an effect mediated by median raphe receptors) was increased in FH rats. In most FH but only a few SD rats a special neurological syndrome, clonic movement of the masseters and in-and-out movement of the eyeballs, was induced by 8-OH-DPAT, and this behaviour like other effects of 8-OH-DPAT, was completely blocked by pretreatment with the 5-HT(1A) receptor antagonist WAY-100635. In SD rats fluoxetine (10 mg/kg/day, i.p.) caused a moderate inhibition of 8-OH-DPAT-induced hypothermia, an effect mediated most likely by hypothalamic 5-HT(1A) receptors, (-19% and -40% after 7 and 16 days of fluoxetine, 24 h after the last injection, respectively). In FH rats fluoxetine caused a rapid and complete reduction in the 8-OH-DPAT-induced hypothermia (-65% and -91% after 7 and 16 days of fluoxetine, respectively). Fluoxetine caused no change in lower lip retraction but a reduction in the masseter-eyeball syndrome in both SD and FH rats. Our data provide evidence that in FH rats, median raphe 5-HT(1A) receptors are hypersensitive, and the hypothalamic 5-HT(1A) receptor desensitization, caused by SSRI antidepressants, is faster and more complete. These data support the notion that chronic treatment with SSRIs induces a desensitization of some 5-HT(1A) receptor populations, and impaired 5-HT storage and reuptake may accelerate this process.

PMID:   11226808   [PubMed - indexed for MEDLINE]

 


Edited by Area-1255, 03 April 2015 - 11:38 PM.

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#20 lourdaud

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Posted 06 April 2015 - 06:46 PM

What's the best source for Shilajit? Seems expensive..


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#21 lourdaud

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Posted 24 April 2015 - 11:31 AM

I scanned through my 23andme results and just as I suspected I have a mutation at the HTR2A gene. I think this partly explains many of my problems and is the reason why I react so well to psychedelics.

 

Stimulants do treat my ADHD but it's a stupid way of doing it - just as letting go of the brake is better than pushing the gas pedal harder while you're driving, reducing serotonin should be better than directly increasing other neurotransmittors.

 

The question is: how can this be done effectively?

I've ordered Shilajit but the only other stuff I can think of is cyproheptadine, BCAA and glycine/gelatin. Unfortunately none of this have been very effective..



#22 OneScrewLoose

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Posted 27 April 2015 - 03:34 AM

Reducing serotonin in order to have effects opposite SSRIs, is, I'm sorry, a laughable idea. The effects of SSRIs are complicated and not well understood, they do much more than simply increase serotonin.

Maybe you can state your goals and I can give some recommendations?


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#23 Area-1255

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Posted 27 April 2015 - 04:02 AM

Reducing serotonin in order to have effects opposite SSRIs, is, I'm sorry, a laughable idea. The effects of SSRIs are complicated and not well understood, they do much more than simply increase serotonin.

Maybe you can state your goals and I can give some recommendations?

Their mechanism of action is to inhibit the serotonin transporter, which leads to increased/enhanced serotonin in the synapse, any other effects are based on pathways that serotonin influences...which may include BDNF upregulation, endorphin changes, enzyme and amino acid uptake changes etc...it's also possible that digestive enzymes are altered by SSRI, considering that most of serotonin is in your gut, now that change affects other natural chemicals and the breakdown of them.

 

Additionally, some SSRI's possess neurosteroid related properties or the ability to interact with sigma receptors.

http://area1255.blog...on-of-data.html


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#24 Area-1255

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Posted 27 April 2015 - 04:06 AM

I scanned through my 23andme results and just as I suspected I have a mutation at the HTR2A gene. I think this partly explains many of my problems and is the reason why I react so well to psychedelics.

 

Stimulants do treat my ADHD but it's a stupid way of doing it - just as letting go of the brake is better than pushing the gas pedal harder while you're driving, reducing serotonin should be better than directly increasing other neurotransmittors.

 

The question is: how can this be done effectively?

I've ordered Shilajit but the only other stuff I can think of is cyproheptadine, BCAA and glycine/gelatin. Unfortunately none of this have been very effective..

Cyproheptadine is garbage, it has additional anti-cholinergic and anti-dopaminergic effects that diminish any benefit that would be seen with serotonin blockade...if it were just a serotonin antagonist - then it would be useful.


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#25 zaratoo

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Posted 27 April 2015 - 04:42 AM

I got a piece of Mumiyo, about 40g. I believe mine is from Altai. Cut several 200-400mg bits off it and gonna take 2 a day. Just half an hour ago I put 330mg into my coffee with milk and drank for the first time. Will do circa 500mg a day for a while..

 

BTW found this thread excidently on the half way of my cup =)                               


Edited by zaratoo, 27 April 2015 - 04:44 AM.


#26 OneScrewLoose

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Posted 27 April 2015 - 04:53 AM

 

Reducing serotonin in order to have effects opposite SSRIs, is, I'm sorry, a laughable idea. The effects of SSRIs are complicated and not well understood, they do much more than simply increase serotonin.

Maybe you can state your goals and I can give some recommendations?

Their mechanism of action is to inhibit the serotonin transporter, which leads to increased/enhanced serotonin in the synapse, any other effects are based on pathways that serotonin influences...which may include BDNF upregulation, endorphin changes, enzyme and amino acid uptake changes etc...it's also possible that digestive enzymes are altered by SSRI, considering that most of serotonin is in your gut, now that change affects other natural chemicals and the breakdown of them.

 

Additionally, some SSRI's possess neurosteroid related properties or the ability to interact with sigma receptors.

http://area1255.blog...on-of-data.html

 

 

If it were that simple, then tianeptine, a Serotonin Reuptake Enhancer, would have the direct opposite effects of SSRIs, But it's not, and draining yourself of Serotonin is a silly approach.


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#27 lourdaud

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Posted 27 April 2015 - 10:58 AM

Reducing serotonin in order to have effects opposite SSRIs, is, I'm sorry, a laughable idea. The effects of SSRIs are complicated and not well understood, they do much more than simply increase serotonin.

Maybe you can state your goals and I can give some recommendations?

 

"Have effects opposite SSRI's" - I never said this was my goal?

My goal is simply to reduce serotonin, as I'm convinced it's bad for you, especially in the long run.

If you have any advice I'd be happy to hear them.

 

Cyproheptadine is garbage, it has additional anti-cholinergic and anti-dopaminergic effects that diminish any benefit that would be seen with serotonin blockade...if it were just a serotonin antagonist - then it would be useful.

 

 

Yeah, I know. I do find it useful for sleep every now and then though.

I've tried Paradise Herbs' Shilajit at 1000 mg doses and it does make me feel good. But at these doses it's too expensive. You know any source for bulk powder?

 

If it were that simple, then tianeptine, a Serotonin Reuptake Enhancer, would have the direct opposite effects of SSRIs, But it's not, and draining yourself of Serotonin is a silly approach.

 

Well no, just as SSRI's, tianeptine has several other mechanisms, opioid agonism being one.

 

Do note that I'm not saying low serotonin doesn't play a role in depression - it most certainly does - but I'd rather feel depressed and miserable than be looping on serotonin.

To quote John Stuart Mill:

It is better to be a human being dissatisfied than a pig satisfied; better to be Socrates dissatisfied than a fool satisfied. And if the fool, or the pig, is of a different opinion, it is because they only know their own side of the question. The other party to the comparison knows both sides.

 

To give you some perspective: the type of behavior displayed by upper classes of society; the elegance, the subtlety, the higher levels of intelligence and conscience, most likely reflect low serotonin levels (or rather, a lower ratio of serotonin to other neurotransmitters). Now take the opposite, high serotonin, say in combination with a poor immune system, low metabolic rate, chronic inflammation, and what will you have? Well, a serf/thrall.

 

To refer to Timothy Leary's Eight Circuit Model of Consciousness, as you see, the upper circuits are activated by drugs that alter/lowers serotonergic expression.

 

From an article I found interesting:

Suomi gathered plenty of that evidence himself in the years after his 2002 study. He found, for example, that monkeys who carried the supposedly risky serotonin-transporter allele, and who had nurturing mothers and secure social positions, did better at many key tasks—creating playmates as youths, making and drawing on alliances later on, and sensing and responding to conflicts and other dangerous situations—than similarly blessed monkeys who held the supposedly protective allele. They also rose higher in their respective dominance hierarchies. They were more successful.

 

 

 


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#28 OneScrewLoose

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Posted 27 April 2015 - 10:11 PM

And that eight circuit model of consciousness has what double-blind evidence to show that it is an accurate model of consciousness? We know next to nothing about consciousness. If you want to know more on the topic, I recommend the book "The Mystery of Consciousness" by John Searle. It's one of the few I've seen that talks more about what we don't know than what we do.

You really wanna reduce serotonin? Take methyldopa. It's a L-Amino-Acid-Dexcarboxylase inhibitor, which means it prevents the conversion of 5-HTP to Serotonin and L-Dopa to Dopamine. You can then re-increase the dopamine through something like Selegiline. You'll find you will not be getting the results you're looking for.

Which are what, btw? The notion that serotonin is "bad" for you makes no sense at all. It's a critical neurotransmitter. It has critical functions, not just in the mind, but in the body as well. There are no neurotransmitters that are "bad" for you, just imbalances.


To give you some perspective: the type of behavior displayed by upper classes of society; the elegance, the subtlety, the higher levels of intelligence and conscience, most likely reflect low serotonin levels (or rather, a lower ratio of serotonin to other neurotransmitters).

 

[Citation Needed]


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#29 Area-1255

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Posted 27 April 2015 - 10:15 PM

 

 

Reducing serotonin in order to have effects opposite SSRIs, is, I'm sorry, a laughable idea. The effects of SSRIs are complicated and not well understood, they do much more than simply increase serotonin.

Maybe you can state your goals and I can give some recommendations?

Their mechanism of action is to inhibit the serotonin transporter, which leads to increased/enhanced serotonin in the synapse, any other effects are based on pathways that serotonin influences...which may include BDNF upregulation, endorphin changes, enzyme and amino acid uptake changes etc...it's also possible that digestive enzymes are altered by SSRI, considering that most of serotonin is in your gut, now that change affects other natural chemicals and the breakdown of them.

 

Additionally, some SSRI's possess neurosteroid related properties or the ability to interact with sigma receptors.

http://area1255.blog...on-of-data.html

 

 

If it were that simple, then tianeptine, a Serotonin Reuptake Enhancer, would have the direct opposite effects of SSRIs, But it's not, and draining yourself of Serotonin is a silly approach.

 

Because YOU are thinking too simply, the reason tianeptine doesn't do that, is because it has other effects, such as mu-opioid receptor agonism..so it WOULD have effects opposite - if it weren't for it's glutamate modulation and opioidergic effects.

 

If you are lowering serotonin, you are trending towards increased glutamate , cholinergic transmission and possibly GABA as well...dopamine might be raised indirectly...but tianpetine lowers some forms of glutamatergic transmission ; producing effects that parallel serotonergic anti-depressants in some ways.


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#30 Area-1255

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Posted 27 April 2015 - 10:18 PM

And that eight circuit model of consciousness has what double-blind evidence to show that it is an accurate model of consciousness? We know next to nothing about consciousness. If you want to know more on the topic, I recommend the book "The Mystery of Consciousness" by John Searle. It's one of the few I've seen that talks more about what we don't know than what we do.

You really wanna reduce serotonin? Take methyldopa. It's a L-Amino-Acid-Dexcarboxylase inhibitor, which means it prevents the conversion of 5-HTP to Serotonin and L-Dopa to Dopamine. You can then re-increase the dopamine through something like Selegiline. You'll find you will not be getting the results you're looking for.

Which are what, btw? The notion that serotonin is "bad" for you makes no sense at all. It's a critical neurotransmitter. It has critical functions, not just in the mind, but in the body as well. There are no neurotransmitters that are "bad" for you, just imbalances.


 

 

To give you some perspective: the type of behavior displayed by upper classes of society; the elegance, the subtlety, the higher levels of intelligence and conscience, most likely reflect low serotonin levels (or rather, a lower ratio of serotonin to other neurotransmitters).

 

[Citation Needed]

He never said that serotonin is bad or needs to be eliminated, I merely said it's over rated and it's effects on hormones make it an incorrect target. 

 

For example, which would you rather have?

 

  • Moderate serotonin, but less than optimal dopamine, testosterone etc

 

OR

 

  • LowER serotonin (but not deficient), and high testosterone and pituitary function as well as higher order thinking and cognitive/intellectual sharpness.

 

Everything is about looking at tendencies, and predicting them within your own body. 

OF COURSE serotonin has vital functions, but you don't need that much of it to be happy or sufficient. 

However, people with hormone issues or estrogen dominance will probably find that serotonin being low or high is causing side-effects..and any minor change could create the illusion of issues by that substance due to extracellular sensitivities/intolerance.


Edited by Area-1255, 27 April 2015 - 10:20 PM.

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