5-HT1A/ Serotonin Systems Research

[Ghost]

My last thread for a while...I promise...I've gone all in trying to throw new info onto the forum.

As you all know...I love reading articles, and theorizing/brainstorming/learning through them. This thread is for that. Any article you find, or any question you have regarding 5HT1A receptor or the serotonin system in general.

To start things off...

VERY GOOD READ. Not gonna lie...parts of it are way over my head...but I understand most of the serotonin stuff. I figure if I want to go into this stuff as a career, I might as well learn it now, right?

It's a very dense article, and one that does a good job of explaining some basics of the serotonin system, and the affects of agonists/ antagonists, as well as SSRI's. I'm 3 pages in, and there are 15 pages of info. So...I've barely scrapped the surface. But...It'll give me a weekend project. I'll post anything else from it that I find usesful.

http://faculty.virginia.edu/brain_map/L3F/Untitled.pdf

This first part is already pretty well known. 5ht1a controls Oxytocin, Prolactin, and other things listed below.

" It's well-documented that
5-HT1A and 5-HT2 , are involved in the regulation of pituitary
gland hormones under basal conditions and stress stimulation. The
studies were performed in male rats and focused exclusively on AVP,
oxytocin, CRH, adrenocorticotropic hormone (ACTH) and prolactin
(PRL)"

Now, here is a place where I can see receptors regulating the gene expression of other hormones...is it possible that SSRI's regulate 5ht1a (HTR1A) gene expression by messing with something else in the brain? This is something that I hadn't even considered before. I don't know how we'd ever test this...but it's just a passing thought.

"The involvement of 5-HT and 5-HT receptors in the regulation of:
i. The gene expression of hypothalamic hormones
ii. The hypothalamo-adenohypophysial system (prolactin and
ACTH)
iii. The neurohypophysial system (vasopressin and oxytocin)
B. The involvement of 5-HT and the 5-HT receptors in the stress induced
neuroendocrine responses
C. The relative importance of some distinctive central nuclei in the
basal and stress-induced hormone secretion
D. The metabolism of 5-HT in the hypothalamus and the dorsal
raphe nucleus"

Now, I know that MAO inhibitors work by decreasing M/O. If PSSD is caused by extra 5-ht in the synapse...then would adding more MO help PSSD? are there MAO enhancers? How do you raise these levels?

"The degradation processes
are very fast due to a large surplus of monoamine oxidase"

We already know about the following two quotes.

"Serotonergic cell bodies are located in the brain stem anatomically
divided into nine groups, designated B1-B9, of whom the most important
are the dorsal raphe (DRN, B7) and the median raphe nucleus
(MRN, B8)"

"5-HT1A and 5-HT1B receptors are in addition located presynaptically
as autoreceptors "

Yep...This describes that receptor sensitivity can be controlled by a drug, and this is something that we already know as well.

"Local differences
in the regulation of receptor sensitivity and abundance following
prolonged drug administration or stress-induced changes are responsible
for the differences in therapeutic effects or side effects of
different 5-HT antagonists and agonists"

This is where the affinity charts some in. This is for agonists...

"5-CT . . . . . . . . . . . . . . . . . . . . . . . . . . 9.5 (159) 8.3 (159) 3.5 (159) 6.2 (157) 5.5 (159) 9.5 (243) 9.5 (326)"

This actually has the highest affinity as an agonist at the 5ht1a. It is also high at the 5th1b, 5a, and 5ht7.

It does so much better as an agonist than 8-OH-DPAT at most sites, but only slightly more affinity at the 5ht1a...

"8-OH-DPAT . . . . . . . . . . . . . . . . . . . . 9.2 (254) 5.1 (254) 5.2 (254) <5 (254) 7.0 (243) 7.5 (326)"

So that's the agonist route. Source of the problem. Better in my opinion. You want pre-synaptic activation to be normal, and not just hide less of it with blocking post-synaptic activity of 5ht.


But..if you wanna beat around the bush, and think that antagonism of the post-synaptic side is right... Way-100635 will be your best option...It's selective 5ht1a antagonist (basically), and really is quite strong

WAY-100635 5-HT1A . . . . . . . . . . 8.9 (106)

The only one that ties it is

NAN-190 5-HT1A . . . . . . . . . . 8.9 (357) 6.2 6.6 (357) 6.2 5.9

and it also antagonizes other receptors. In my opinion, you'd want to leave well enough alone, and not touch the other receptors unless you think that's a much better option.

This is all I have for now. Will keep posting updates.