+ 10 Estrogen Effects on Serotonergic and Dopaminergic Neurotransmission (Estrogen in the Brain)
~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...
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AREA, I always appreciate the stuff you post, thanks
Area-1255Glad you enjoyed it brotha!
Area-1255https://area1255.blogspot.com/2016/11/masteron-vs-andractim-for-estrogen...
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
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!
Area-1255What did Selegiline do to your blood pressure, increase or lower it?
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.
Area-1255I've heard a lot of good things about Selegiline, do you get a script for it or order online? My only concern with Selegiline (Deprenyl) VS Rasagiline is that Selegiline converts into a methamphetamine metabolite, particularly levomethamphetamine (l-methamphetamine) which is the more adrenergic (adrenaline promoting) fraction of methamphetamine.
Lemke, Thomas L.; Williams, David A, eds. (2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. p. 434. ISBN 1609133455.
https://www.ncbi.nlm.nih.gov/pubmed/1658311
https://en.wikipedia.org/wiki/Selegiline#Levoamphetamine_and_levomethamp...
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.
Area-1255Nice man! Yeah Selegiline sounds like some good stuff. Gonna have to try it soon.
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

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.
LMFAO!!!
FLASH IS BACK ;)
he was a Dickl with most people bro...thought everyone was below him
Area-1255Lol.
Area-1255It's just showing that Estrogen has profound effects on dopamine and serotonin, it generally promotes dopamine release and serotonin, though in some cases, and more specifically, in some brain regions it may deactivate dopaminergic and / or serotonergic functioning.
It's simply another reinforcement, that E2 should be kept in the proper ratio/proportion with Testosterone in order to maintain ideal executive and declarative memory functions as well as for intellectual thinking and creativity.
It also further shows why Estrogen is involved with libido, and that it involves dopamine:serotonin ratio and interactions between the two.
Area-1255http://area1255.blogspot.com/2016/04/best-sexual-enhancement-supplements...
Area-1255http://area1255.blogspot.com/2016/02/does-inhibiting-dht-raise-increase....
Area-1255http://www.ncbi.nlm.nih.gov/pubmed/7704444
http://www.ncbi.nlm.nih.gov/pubmed/23340667
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
Area-1255Right, the alpha-self is still there and thus confidence and all other desirable traits generally still in tact - it's just extra 'oomph' disappears along with pheromonal responses..e.g the erotic walking seeker missile self.
Which again, makes sense, if 5-HT1A and 5-HT1B receptors upregulate in response to estrogen deficiency, then that means OUR response to female pheromones will be ablated/hindered in addition to libido.
Read this study - it should be an important highlight for this entire write up .
http://www.ncbi.nlm.nih.gov/pubmed/11965359
In other words, with deficient estrogen, one should should expect our testosterone to not rise in response to female presence and thus sexual motivation is dulled due to 5-HT1A upregulation.
Then with the 5-HT1B receptors being upregulated, sexual motivation and orgasm capacity is blunted including initiation.
THUS, in theory, we could eliminate or at least partially reduce the low libido side effect of estradiol deficiency as it applies - alternatively by using yohimbine (a 1B antagonist) plus a 1A antagonist..but unfortunately, there are no 1A pharms available except through a lab...so stuff like lecozotan or robalzotan would be ideal in combination with yohimbine and possibly a dopamine agonist as well.
Very interesting brother. Thanks
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
RustyhookerExplains the correlation between high and low estro having similar side effects. Many folks post their sides and in many occasions only a blood test can separate truth from trouble shooting.
Sex drive has also been interesting in terms of individual responses to high or low estrogen. Clearly, the unique differences between individuals create a real need to "map" our bodies with continued testing and note taking.
Area-1255Oh yea! Severely low E2 seems to produce joint clicking and a diminished reward circuitry - as in motivation for reward related tasks..although some seem to be immune to this effect. I think I'm a little low on the sides myself, but...I definitely notice a difference.