role of catecholamines in entactogen effects

[neurotic]

so both 5HT1Ar antagonists and an oxytocin receptor antagonist prevented prosocial effects of MDMA (http://www.ncbi.nlm.nih.gov/pubmed/17383105). seems plausible that this OX release is key in the entactogen effects... MDMA raises CENTRAL levels of oxytocin too so i guess it settles it

though the indirect activation of the 1A receptors and further OX release apparently isn't sufficient for the entactogen effects*, as seen with anedoctal reports on selective and selective-ish 5HT releasing agents being uninteresing... catecholamine release is necessary too, and i remember sekio mentioning preventing NE release from MDMA prevented its effects...

is it correct to think that NE plays an important role in the effects? probably something with the amygdala i'd guess (just found a promising paper about NE in the amygdala and fear extinction... the content will probably be beyond my comprehension though)

how could whatever NE is doing the amygdala connected to the oxytocin release? because, y'know i don't think NE releasers alone would be helpful in e.g. fear extinction training

and: * i wonder what 8-OH-DPAT feels like. someone try it already!!!

oh boy, MDMA seems like one HELL of a serendipitous drug, i mean, if in history humans were trying to find something like it through intelligent drug design...

 

[serotonin2A]

My gut feeling is that you can't really make the leap from animal behavioral experiments to the human condition with regard to the entactogenic effects of MDMA. What is being measured in animals may not reflect the things that make MDMA interesting in humans.

8-OH-DPAT generalizes to MDMA in rat drug discrimination studies, which may reflect the fact that DPAT acts off-target as a serotonin releaser. But it is highly unlikely that DPAT would be an enjoyable drug. Most serotonin releasers are not very fun (fenfluramine, MBDB, MDAI, PMA, TFMPP).

 

[neurotic]

Wait 8-oh-dpat is a Selective 5ht releasing agent? Did not know that. This kills my extrapolation from the study since it can mean that SSRAs will have prosocial effects in rodents, and consequently, that these effects are not indicative of human entactogen effects, like you said.

Hmmm... A study on SSRAs and fear extinction would be interesting.

 

[serotonin2A]

Wait 8-oh-dpat is a Selective 5ht releasing agent? Did not know that. This kills my extrapolation from the study since it can mean that SSRAs will have prosocial effects in rodents, and consequently, that these effects are not indicative of human entactogen effects, like you said.

Hmmm... A study on SSRAs and fear extinction would be interesting.

I said "DPAT acts off-target as a serotonin releaser". It is definitely not a selective 5-HT releasing agent. It used to be used as a selective 5-HT1A agonist, but was subsequently shown to bind to 5-HT7 and to release 5-HT (among other effects).