SARMs and AR in the brain; Why do I feel so fucking good?

I'd like to take you all on a ridiculously long and complex journey through the next few weeks. Exploring AR/SARM relations in the brain. A lot of this is just exploration, and I don't assume to have the end all knowledge for anything, let alone neurochemistry. That being said, let's Google some shit.

Often times when thinking about muscle and strength gain we forget about the mental anguish it may take to push ourselves to the next level. Recently (and personally), I've noticed a trend in users suggesting that their SARMs have to be working almost immediately. We know, however, that we don't receive the full benefits of our SARMs until it's fully saturated our plasma around 2-3 weeks. The next logical question in my opinion would be, what role do androgens/AR play in our mental health and motivation? At first, this question may be easy to glance over, but when putting SARMs in relation to AAS one has to wonder, why don't our users seem to experience the same mental fatigue and depression post cycle that many AAS users face?

This week we'll start with something everyone is familiar with, Dopamine. Neurotransmitters in our brains are constantly in communication with each other, regulating every function in our body. Selective as they may be, SARMs are intended to only target the androgen receptors in our bones and muscles. When we talk about how selective they are however, we aren't being quite exact. In fact, RAD has been shown to have neuroprotective properties as soon as one hour after administration (Anusha). Taking from this, we can assume that not every SARM is limited to binding to our muscles and bones, and in fact does pass in to the AR in our brains.

Androgens have a long history of being effective regulators of mood, which is consistent with the distributions of AR and ER within the limbic system and prefrontal cortex.

The hypothalamus is the area of our brain responsible for hormone release through it's control of the anterior pituitary. Together, they create releasing hormones such as Dopamine, GHRH, and GnRH, to name a few. These hormones are then sent to the posterior pitauitary, and just kind of chill out until you actually need them. Already, we have two points in our brains that AR can effectively regulate Dompamine. Although limited data exists on androgen receptor distribution in the human brain, current studies suggest patterns follow similar to rodents and primates (Pelletier).

A study in 2012 revealed "complex effects of gonadectomy on antagonist-stimulated PFC DA levels that together with the anatomical data above suggest that androgen stimulation of PFC DA systems does engage glutamatergic circuitry and perhaps that of the AR-enriched glutamatergic projections from PFC-to-VTA specifically" (Abuele). Now, hopefully you boys still have, well, your boys, so we can assume that these effects might not be so drastic for us, but they're still interesting to note. Looking at the graph of castrated mice supplemented with test prop, we can clearly see a wonky relationship in PFC projections to Dompamine actions in castrated/non castrated rats. As soon as 20 minutes after application, we can see a reaction in projections sent from the PFC to the hypothalamus, effectively regulating dopamine interactions and production. For now, we'll set aside the implications of stimulated glutamate and just focus on dopamine.

So what the fuck am I trying to say, you may ask?

Basically, I believe that a certain amount of our added volume or intensity while on PEDs can absolutely be attributed to more than just placebo. I believe that our friends using AAS suffer from an overload of these pathways while on cycle, constantly upregulating dopamine actions throughout the brain. I believe that due to the selective nature of SARMs, we still receive many of those benefits, but not at the expense of the overload test may give. I think this can attribute to the week 1, or even day 1 success stories we hear regarding some SARMs. Potentially, this almost immediate response to AR activation in the brain may allow you to be able to break through previous barriers mentally, and even feel good while doing it.

It's more than obvious to me that the selectivity of SARMs is not limited to muscle and bone, and that AR activation is bound to occur in the Hypothalamus as well given it's relation to the prefrontal cortex. Given the density and location of our AR, I believe we see an almost immediate response from our SARMs, allowing us to feel a little better, think we look a little better/full, push a little harder that first week in the gym, and all around think our SARMs have 'kicked in' sooner than their build up of plasma toxicity.

The relationship between chemicals in the brain is fucking insane, and I'm obviously no expert. I do however look forward to exploring this further in the coming weeks, as it's just too dense a subject to tackle at once.

-Pelletier G. 2000 "Localization of androgen and estrogen receptors in rat and primate tissues"

-Anusha J. 2014 "Selective Androgen Receptor Modulator RAD140 Is Neuroprotective in Cultured Neurons and Kainate-Lesioned Male Rats"

-Abuele T. 2012 "Androgen Influence on Prefrontal Dopamine Systems in Adult Male Rats: Localization of Cognate Intracellular Receptors in Medial Prefrontal Projections to the Ventral Tegmental Area and Effects of Gonadectomy and Hormone Replacement on Glutamate-Stimulated Extracellular Dopamine Level"