Serotonin Deficiency & Neurotoxicity

[Mr Blonde]

OK, I know that it's no longer thought by most people that serotonin deficiency is the sole/universal cause of depression, but I have been to at least one pharmaceutical site where they advocate that as one of the major causes.

I also know that most current and widely accepted theory on MDMA's neurotoxicity is the idea that when the serotonin is eventually removed from the synapse by the serotonin transporters, when you start coming down, the much lower levels of serotonin allow the dopamine which is still in the synapse or perhaps attached to receptors to bind to these transporters. This is bad news because:

a) Dopamine itself is bad for the serotonin cells, and...
b) The MAO's that break down most of the serotonin that is taken out of the synapse also break down dopamine into Hydrogen peroxide, which caused oxidative damage to the serotonin cell.

Finally, my questions:

1) If you suffer from clinical depression that is perhaps caused by serotonin deficiency (assume non-drug related), then is it possible to suffer from brain damage somehow as dopamine is more likely to be uptaken (if that's the right term) from the synapse in place of serotonin?

2) How do you pronounce dopamine?

3) How do your pronounce norepinephrine?

 

[Splatt]

doh-pah-meen
nor-eh-pin-eff-reen (i think?)

 

[phase_dancer]

Firstly addressing the initial points you raised. I read mountains of stuff on this a couple of years ago, but its very well possible more recent findings have altered this proposed model. IIRC, and if the then postulated mechanisms still hold, dopamine is sometimes picked up by SERT in normal situations i.e. irrespective of whether or not there is a deficiency in 5HT. Inside the cell body MAO oxidises dopamine and produces H2O2, which is also produced when serotonin is oxidised by MAO.

Normally (no 5HT deficiency) other mechanisms protect against the free radical actions of peroxide and the highly reactive species formed by H2O2. The problem seems to arise when the neuron is deficient in 5HT. The free radicals then migrate to the mitochondria where they attack the membrane which effectively destroys the cell.

Dopamine is released as a response to MDMA activities on 5HT from regulatory neurons such as GABA, however, dopamine may not necessarily be the only player here, as again IIRC, tests where dopamine release was inhibited concurrently with MDMA induced 5HT depletion also resulted in some neurotoxicity.

1) If you suffer from clinical depression that is perhaps caused by serotonin deficiency (assume non-drug related), then is it possible to suffer from brain damage somehow as dopamine is more likely to be uptaken (if that's the right term) from the synapse in place of serotonin?

No, this would not occur without some chemical "crow bar". Mechanisms exist to regulate 5HT and although it's reasonable to assume levels may fluctuate somewhat in certain regions of the brain with certain conditions (such as depression etc), it's very unlikely that without either a disease state or a toxin like MDMA being present, that these intracellular 5HT levels would be reduced so significantly. Remember, it's a depleted state that appears to make the neuron prone to free radical damage. Normally the neuron has reserves of 5HTP to compensate for normal endogenous fluctuations in serotonin

 

[Teddles]

norepinephrine and epinephrine is the American word for noradrenaline and adrenalin because of patent issues. Same reason paracetmol is called acetaminophen in most OS sites and medical books.