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Saturday, January 30, 2016

What Determines 5-HT5A Receptor Expression? (How to Regulate 5-HT5A Receptors)


Previously, I had elaborated on how ''mysterious'' the human serotonin 5-HT(5)A Receptor is. In Particular, how it's role as a GPCR (G-Protein Coupled Receptor) results in the relative decrease of the vital second messenger cyclic AMP (cAMP) (1), an effect that normally, would result in Reduction of some forms of nervous system stimulation, yet, despite reducing calcium mobilization - it plays a Primarily anxiogenic role (2) (3) (4); including in LSD's not-so-pleasant effects (5) (6) (7)



  1. This means that, activation of the 5-HT5A Receptor , seems to reduce N-Type Calcium Channels as a direct consequence of it's actions on G-Protein's (reducing cAMP) (8).
  2. Yet, it , when activated, increases Anxiety-like behavior - especially ''STARTLE'' resultant from sudden noises and changes in environment (9) (10).
  3. If one is too sensitive to environmental cues and projections - one is less likely to become social and outgoing; veering into the direction of social aversion is consistent with human studies linking alterations in this receptor to Schizophrenia and Depression / BiPolar (11) (12) (13) (14).


With all of this being taken into Account - it makes perfect sense to find ways to downregulate the 5-HT5A Receptor ; a receptor I am officially coding as the ''Receptor of Exploration"...for reasons I will get into More later in this Post....



  • In Regards to ANXIETY, 5-HT5A Receptors act as ~AutoReceptors~ that inhibit/decrease Serotonin release in key Area's of the Brain (15).
  • They also appear co-localized with GABAergic neurons; leading to a decrease in GABAergic transmission when activated (16) (17).
  • 5-HT5A Receptors affect exploratory behavior on multiple levels - by SMELL, SIGHT, HEARING...imagine the Euphoria of entering into a new Country, or being in a Cave or Mountain somewhere - well, the 5-HT5A Receptor ''regulates'' the processing of these smells as well as the retention of associated visual cues...too much 5-HT5A Activation creates an internally preoccupied state which leads to reduced capacity for cognitive flexibility and psychotic-like features - thus, we are no longer interested in novel environments and smells , and a Zest for traveling or moving, really, at all, disappears...thus providing a role in 5-HT5A-mediated-anxiety-Induced Anhedonia... (18) (19) (20)...

NOW..HOW ON EARTH DO WE REGULATE THIS ODD, RECEPTOR...

  • Oddly enough, LEPTIN seems to influence 5-HT5A Expression; specifically, the administration of which - DECREASES 5-HT5A in the Hippocampus (21), so there's something.
  • Estrogen; the female sex hormone - decreases 5-HT5A Receptors in the Hippocampus but increases them in the Pituitary (22) (23).

The answer is in the Puzzle itself - if we can control the amount of Leptin we might have a viable way to methodically 'deregulate' the 5-HT5A Receptors...

  • We'd have to increase the APPETITE-SUPPRESSING-HORMONE LEPTIN (Satiety-Producing).
  • Increase Free Testosterone (FT/FTT) to ALLOW for *some* Brain Estrogen to reduce the concentrate of the 5-HT5A Receptors in Memory-Related-Brain-Region/s (Hippocampus).

IT REALLY IS THAT EASY..

  1. Try L-Histidine + Folate; histamine is shown to both increase leptin levels and accelerate the response to Leptin - especially in the HYPOTHALAMUS; where it COUNTS (24) (25) (26) (27).
  2. A Free Testosterone booster like Tongkat Ali WITHOUT an Anti-Estrogen may help facilitate the effects noted - but ONLY if you use the 1st Method as Well!!




**OTHER NOTES**
  • 5-HT(5)A Receptor is HEAVILY Involved in Serotonin's REDUCTION In Sensory Activation; Skin/Thermal ETC... (1) (2) (3)
  • 5-HT5A Receptors may Play a larger Role in Endocrine Activity than Just Vasopressin/Oxytocin Modulation... (4)
  • VALERIAN EXTRACT Acts as a ((Partial Agonist)) at The Receptor. <see here>



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