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Comment · Tue, January 28, 2014

Effects of sustained serotonin reuptake inhibition on the firing of dopamine neurons in the rat ventral tegmental area

What they were answering

[deleted] · 1 points

That first one's 5-HT1B, not 2B! This reminds me of my excitement for future research on 5-HT1E/F and 5-HT5 receptors.

The 5-HT2B receptor is intriguing. It might be a useful therapeutic target as an agonist centrally (I don't know much about it, honestly!), but definitely not peripherally (on the heart).

I like that style of thinking, knowing which receptor modulates which effects can lead to a better grasp of what therapeutic targets should/not be avoided, and why, and specifically where certain adverse effects might originate. I've found it a very helpful approach in researching the different dopamine receptors and plus, it's a lot more specific than reuptake inhibition --> more serotonin --> all these different effects, it's much more specific!

Speaking of MDMA... hm, can't think of the chemical's name at the moment. It's a non-neurotoxic monoamine releasing agent, not self-administered by rats. It sounded like an interesting drug, but I can't think of the name. Hopefully I come across it soon. Maybe you know it!

u/MisterYouAreSoDumb

Yeah, I edited it when I noticed. Still, the effects are due to MDMA's 5-HT release in those regions, which non-selectively binds to the various receptors. So the idea is that agonism/antagonism of various 5-HT sub-receptors in the VTA is responsible for activation/deactivation of the mesolimbic dopamine system.

And yes, it is so much more specific than meets the eye. The various sub-receptors are distributed in differing ratios in the various brain regions. Since different substances cause releases of catecholamines in different regions, they lead to different effects. It's not like all serotonin releasing agents lead to the same 'magic" so to speak. It can also help us to understand the changes in effects when we combine substances, like MDMA and amphetamine. It's not just a simple, more 5-HT and DA. It's very region-specific, which causes a lot of cascading changes to the effects.

Are you thinking MMAI? Or are you looking for a less selective monoamine releasing agent?

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