Comment · Thu, August 15, 2013 · Ceretropic
Role of Monoaminergic System in the Etiology of Olive Oil Induced Antidepressant and Anxiolytic Effects in Rats.
What they were answering
Parent comment was not in the public dump (deleted, or never archived).
u/MisterYouAreSoDumb · Ceretropic
Look at tianeptine. It's a selective serotonin re-uptake enhancer. It leads to less extracellular 5-HT, consequently leading to up-regulation of postsynaptic 5-HT receptors. Most people report euphoria and mood lift after taking it.
It's just as interesting as Saint John's Wort, which is a mild SSRI. However, SJW leads to up-regulation of 5-HT receptors via modulation of the sodium channels. It does not actually bind to the SERT. One would think that increased extracellular 5-HT would lead to down-regulation, as is seen in traditional SSRIs. However, we see the opposite.
So we need to be looking at the individual mechanisms more closely. One would think that since hyperforin (SJW) mediates the re-uptake inhibition of the SERT from presynaptic mechanisms, and leads to increased extracellular 5-HT, that the only 5-HT receptors that would be up-regulated would be presynaptic 5-HT2A. However it also up-regulates postsynaptic 5-HT1A without any change in receptor affinity, and postsynaptic 5-HT2A!
St. Johns wort (Hypericum perforatum)- a review of the current pharmacological toxicological and clinical literature-_a_review_of_the_current_pharmacological_toxicological_and_clinical_literature.pdf.html)
>Hypericum promotes adaptive
changes in receptor function often observed during con-
ventional antidepressant pharmacotherapy, including: (a)
downregulation of cortical β -adrenoceptors without a
change in receptor affinity (Müller et al. 1997), (b) **upregulation of 5-HT1A postsynaptic receptors without a
change in receptor affinity** (Müller et al. 1997; Teufel-
Mayer and Gleitz 1997), and (c) **upregulation of 5-HT2
receptors** (Müller et al. 1997). Most conventional antide-
pressants are known to downregulate the expression of
both β -adrenoceptors and 5-HT2 postsynaptic receptors
in the rat brain (Krishnan 1998; Leonard 1992; Peroutka
and Snyder 1980; Sulser et al. 1978). Thus, the finding
that Hypericum stimulates an upregulation in 5-HT2 re-
ceptor expression is in contrast to what is known about
the action of TCAs or SSRIs.
So the mechanisms are not as simple as: increase extracellular 5-HT and be happy, decrease extracellular 5-HT and be sad. It would seem to be much more complicated than that.