aced126
Bluelighter
- Joined
- May 18, 2015
- Messages
- 1,047
Amphetamine and MDMA primarily work as monoamine releasers, not uptake inhibitors. Most DA uptake inhibitors lack psychostimulant activity (e.g., GBR 12909, benztropine). Cocaine and methylphenidate are unusual cases, and they may actually release dopamine through DAT.
Serotonergic transmission is regulated by autoreceptors to keep it within a very specific range. So if you block reuptake of serotonin, the cells compensate by reducing their firing rate and releasing fewer transmitter molecules per impulse. I'm not saying that there isn't any change in 5-HT transmission after acute administration of SSRIs, but the increase is substantially blunted by reduced firing and transmitter release. Acute paroxetine is certainly not perceived as being similar to MDAI or MBDB.
By what mechanism does autoreceptor activation result in reduced firing rate?
Also if this is so, then it begs the question of how cocaine and derivatives, and methylphenidate and derivates induce psychostimulant activity despite being reuptake inhibitors. Why isn't more research going into this?