Massive reply. Soz.
somebody source or correct me if im wrong but..
i believe that your neurons down regulate to counter act the excess of serotonin. over time your brain becomes more defensive of mdma so to speak because its less sensitve to the excess serotonin it has all the time.
hers what the receptors look like
So they would actually pull away from each other if its overstimulated by seretonin
People also get neurotoxic cause too much mdma causes unused neurotansmitter to break off into free radicals which oxidise and damage your axons cause of the peroxide dryin em up
interestin readin
http://www.dancesafe.org/slideshow/intro.html
Those aren't receptors, they are axons, which is where the neurotransmitter or hormone (ligand) is released from. The receptors are on the body of the neuron or the dendrites, which are those little tentacles sticking out of the second neuron.
An analogy: The ligand is the key, the receptor is the lock and the neuron is the door. In order to get the door to open, you need to put a key in the lock to open it. That is like getting the neuron to fire. But unlike a door, the neurons have different types of receptors which make the cell do something else. For example, to get the neuron to stop firing. Or perhaps turn a gene on or off. Maybe make the cell burn energy faster. I'll get back to receptors in a sec.
Anyway, a lot of the neurotoxicity studies have been done on animals using large (binge) doses of MDMA. Sometimes it's even called a 'neurotoxic dose of MDMA'. And that's what the picture Master posted is showing. But this isn't what causes tolerance (aka losing the magic) because animals given a non neurotoxic dose (aka does not make the axon all shriveled up like that) still lose the magic. Why?
No one *really* knows. One idea is that the serotonin receptors are down regulated. Receptors can be upregulated (more come to the surface of the cell) or downregulated (taken into the cell). Kind of like removing the lock and door handle from the door. Or they can be inactivated in different ways. That could be like changing the shape of the lock so the key can no longer turn.
There are also two kinds of receptor. Before I wrote about receptors which were on the soma and dendrite of the neuron. Those are called 'post synaptic' receptors and they are the ones that make the cell do something (or stop it from doing something). But there are also receptors on the axon of the neuron releasing the neurotransmitter. Those are called either 'autoreceptors' or 'presynaptic receptors'. They are called autoreceptors because it's the cell doing something to iself. It usually works as negative feedback. It's so the cell knows when to stop making and releasing serotonin. And when do you stop it? When you've released the serotonin, simple. So that released serotonin will also activate the autoreceptor, which tells the cell to not release anymore.
If there are more autoreceptors then post synaptic receptors, then the cell will probably release less serotonin and for a shorter amount of time when asked to. MDMA could be causing the ratio of these receptors to change, so that autoreceptors are up regulated and the post synaptic ones are down regulated. Or the other way around - there are 14 different types of serotonin receptor (eg 5-HT1a, 5-HT2a, 5-HT2c, 5-HT7), some are inhibitory (turn cell off) others excitatory (turn cell on). This is a hypothesis of how it all works, and a similar principle is behind how SSRIs work. After not taking MDMA for a while, the ratio should go back to normal and you get the magic back. So magic loss shouldn't be permanent. Yay! There is some interesting research going on at the moment into getting the magic back after MDMA abuse in rats. Unfortunately this is involving injecting a selective 5-HT1a antagonist (WAY-100,365 if you want the name of it
) into the raphe nuclei where most the autoreceptors are. But unfortunately, that's not going to help us today.
But my big question is - what determines the 'normal' ratio of the receptors? Is that genetic? We know that people naturally have a huge range of serotonin activity and also the same for other neurotransmitters without it have any effect on behaviour. Why?
