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+ 10 Estrogen Effects on Serotonergic and Dopaminergic Neurotransmission (Estrogen in the Brain)

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~I declare I am the rightful owner and publisher/writer of Area-1255 and this following article~

This is a summary of how estrogen, including that derived from or converted from testosterone, by means of aromatase, affects central 5-HT (Serotonin) and dopaminergic neurotransmission.

In the references you will find specific brain region alterations induced by estrogen, and how this may correlate to brain function.
This is all relevant if you want to achieve optimal brain health - including intellectual capacity and general cognition.(!)

[*]Estrogen downregulates somatodendritic 5-HT1A (!) autoreceptors (presynaptic) in the raphe nuclei, leading to enhanced serotonin release in these areas, however, it also increased cortical post-synaptic 5-HT1A receptors - which can induce cortisol and prolactin release and blunt sexual functions(!). (However, estrogen decreases hypothalamic 5-HT1A receptors(!)

[]Estrogen also downregulated 5-HT1A in the limbic areas(!).
[
]Estrogen also downregulates 5-HT1A receptors in the amygdala, hippocampus, perirhinal cortex, and motor cortex (!) , but when combined with progesterone, the 5-HT1A receptors in the hippocampus increased, with no change in other areas.
[]Estrogen also stimulates a significant increase in the density of 5-hydroxytryptamine2A (5-HT2A) binding sites in anterior frontal, cingulate and primary olfactory cortex and in the nucleus accumbens, areas of the brain concerned with the control of mood, mental state, cognition, emotion and behavior(!) (!). This can lead to excitation, anxiety, and potentiation of hallucinogenic drugs.
[
]Estrogen increases SERT (serotonin reuptake transporter) (!) - leading to enhanced reuptake and less serotonin activity in the synapse - this means that although estrogen may increase serotonin through the above autoreceptor modulation , it ends up not mattering too much in the face of less usability. Thus , high estrogen levels rapidly deplete serotonin from the synapse, leading to reduced efficiency and activity of serotonin.
[]Low estrogen levels would create higher serotonin in the synapse, but less receptors , mainly of the excitory types to bind to. One could presume, that both high and low estrogen would reduce positive effects of SSRI-antidepressants, and increase negative side-effects.
[
]Estrogen competitively inhibits serotonin 5-HT3 receptor activity.(!)(!)
[]Estrogen stimulates the expression of serotonin 5-HT4 (causing excitation and prolactin release), 5-HT5A (can disrupt sleep patterns), and 5-HT6 receptor mRNA (causing cognitive disruptions).(!)
[
]Estrogen increases dopamine D(2) receptors in the striatum(!).

Thus, estrogen is largely ANTI-COGNITIVE, ANTI-INTELLECTUAL, and does not really provide much benefit at all in terms of these two areas of neurotransmission ......

However, a small amount of estrogen may be necessary to maintain dopamine receptor expression in men and women(*).
Varying amounts of estrogen per gender, of course....

The greek and roman warriors of old certainly didn't have estrogen dominance - and they were master strategists and intellectuals ---- though I s'pose some of them could be dumb on occasion!

Therefore in terms of serotonergic activity, low estrogen would equate to the following changes.
The fields marked in blue are positive effects of low estrogen, while red is negative, generally.
Purple is neutral, or determined more so by the person.

[]More serotonin in the synapse, due to less SERT (transporters), and thus , lessened reuptake of serotonin.
[
]Increased 5-HT1A receptors in many brain regions, including the hypothalamus, leading to decreased central nitrergic and dopaminergic activity as well as serotonergic neuron activity.
Decreased serotonin 5-HT2A receptor expression. (leading to less cortisol and prolactin, generally good thing)
[]Decreased 5-HT4, 5-HT6, 5-HT5A receptors, especially in pituitary.
[
]Decreased dopamine D2 in the striatum.
[]Increased 5-HT3 receptor binding and activity. (can cause nausea, excitation,pain)
[
]Decreased serotonin production from tryptophan.
[*]MORE MONOAMINE OXIDASE (MAO-A)

THUS ALL ROUND LESS SEROTONIN PRODUCTION AND ACTIVITY WITH LOW ESTROGEN HOWEVER.......IN THE PRESENCE OF NORMALIZING TRYPTOPHAN HYDROXYLASE ACTIVITY - SEROTONIN MAY BE EASIER CHRONICALLY ENHANCED BY LOW ESTROGEN , EXCEPT THAT THE MAIN RECEPTORS SEROTONIN WOULD THEORETICALLY BIND TO WHEN ONE HAS LOW ESTROGEN WOULD BE.

LOW ESTROGEN WOULD MEAN THESE RECEPTORS BELOW WOULD BE MORE AVAILABLE WHILE ALL OTHERS ARE DECREASED.

[]5-HT1A
[
]5-HT1B
[]5-HT1D
[
]5-HT3
[*]5-HT7

THUS, LOW ESTROGEN RESULTS IN DECREASED { ! } rC;Exp (quantitative).

[]5-HT2A/2C
[
]5-HT4
[]5-HT5A
[
]5-HT6

Thus, low estrogen by means of all above may have very broad effects, there may be an increase in some forms of intellectual capacity, but a central reduction in glutamatergic tone and a generally lethargic state - which is more pronounced in women ....however, in men, DHT and other androgens can modulate thinking and cognitive function - however, low estrogen in men, may in some, still lead to depression or the need for caffeine and other stimulants............

IN MY EXPERIENCE, BOTH HIGH AND LOW ESTROGEN CHANGES THE TYPE OF FOOD I LIKE.

When estrogen is on the lower side , nearly undetectable, as with when I was on a cut or aromatase inhibitor, I eat more salty and spicy foods, but when estrogen became high in my large experiments with prohormones, I seemed to cling to carbohydrate type foods and sugary foods!

I do find it easier to eat cleaner with lower estrogen, and also alcohol is not desirable not one bit when estrogen is on the lower side, however, my need for caffeine and stimulants increases at times when estro goes into the undetectable or near undetectable range.

ORIGINAL ARTICLE LINK :: http://area1255.blogspot.com/2014/12/estrogen-effects-on-serotonergic-an...

CBBurrr's picture

AREA, I always appreciate the stuff you post, thanks

hammerheart's picture

Cool. I've researched the matter extensively in the last two years, read tons of scholarly papers and eventually experimented various compounds on myself. This whole thread look like an over-semplification to me Smile

I've been lacking libido since 2012 and I'm also plagued by severe anhedonia, cognitive impairment and more.

The only libido booster that worked for me is selegiline. It takes about two weeks to kick in, and provides significant relief for other symptoms too!

hammerheart's picture

I remember it increased systolic pressure by about 10. I only experienced some ortho hypotension from it when adding levodopa. I believe the stimulating effect was from metabolism to l-meth more than anything.

I'm on caber now btw (0.25 x2), pulled prolactin one month ago and was 54 ng/ml (4-18) for no apparent reason, I did open a thread in the trt section abou this.

hammerheart's picture

Online order... yes l-meth has more affinity for the periphery than the CNS, and almost exclusively affects NE over DA.

Rasagiline doesn't metabolize into l-meth but costs much more.

Next I'm going to try piribedil, a D2 agonist with alpha2-antagonist properties.

Dickkhead's picture

Nice bro. +2

You bumped your own old post, so there must be a reason.

I'm well educated - I have two graduate degrees and two undergraduate degrees from an American Ivy League institution and spent 8 years at the university.

But, these type of scholarly papers give me a headache LOL. I also have the self confidence in my own intelligence to have absolutely no problem in admitting that I am struggling to follow you with some of this stuff because my academic background is in engineering not bio sciences.

So, after that little rant, what is it in ultra simple terms that you are advising me to do here? Or, what is it in really simple terms that you want me to know so that I can incorporate the idea into my diet or training.

I'm just not sure and I don't feel like a dumbass for asking! LOL Smile Smile

TheFlash85's picture

You have a degree in sucking dick. My first ever ban like 3 years ago was for constantly calling you a fraud. Well fuck you.

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kibby's picture

LMFAO!!!

FLASH IS BACK ;)

he was a Dickl with most people bro...thought everyone was below him

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EagerToLearn's picture

I was on 2.5mg pharma letro for 6 month once and except non existent libido I did not notice ANY difference. I had bloods drawn twice and both times my e2 was undetectable

EagerToLearn's picture

Very interesting brother. Thanks

humpnpump's picture

You are right hormones such as estrogen whether high or low levels will stimulate a response to neuro transmitters on what to crave. Regaurdless even when estrogen is controlled and at a normal level we still exhibit mood changes from cortisol, dopamine and prolactin.
I've started keeping nootropics on hand like sulbutamine, phenibut, schizhandra to help with mood swings. L-Theanine is a game changer for high BP and calm energy on stims. Noopept and piracetam keep my cognitive thinking and mood going steady on a daily basis

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