oxytocin release and social drugs

[ManRider]

I was poking around google scholar trying to learn about MDMA and its relationship to oxytocin release when I found this interesting little article:
http://linkinghub.elsevier.com/retrieve/pii/S0306452207001960

The test subjects are just rats of course, but they observe increased social interaction after MDMA administration and then a similar increase in social interation after the administration of another oxytocin releaser, 8-HO-DAPT. The article suggests that for these compounds 5-HT1a agonism is the route to oxytocin release.

This got me thinking about this compound and other similar ones being used as social drugs, both recreationally and for utility to deal with shyness, etc. Does anyone know of this kind of thing being done, or perhaps have thoughts to share on the matter?


Here's the abstract from the article if you don't want to go to the link

The drug 3,4 methylenedioxymethamphetamine (MDMA; ecstasy) has a widely documented ability to increase feelings of love and closeness toward others. The present study investigated whether oxytocin, a neuropeptide involved in affiliative behavior, may play a role in this effect. A moderate (5 mg/kg, i.p.) dose of MDMA increased social interaction in male Wistar rats, primarily by increasing the amount of time rats spent lying adjacent to each other. MDMA (5 mg/kg) activated oxytocin-containing neurons in the supraoptic and paraventricular nuclei of the hypothalamus, as shown by Fos immunohistochemistry. MDMA (5 mg/kg i.p.) also increased plasma oxytocin levels and this effect was prevented by pre-treatment with the 5-HT1A antagonist N-[2-[4-(2-methyoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY 100,635; 1 mg/kg i.p.). The oxytocin receptor antagonist tocinoic acid (20 μg, i.c.v.) had no effect on social behavior when given alone but significantly attenuated the facilitation of social interaction produced by MDMA (5 mg/kg). The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetraline) (8-OH-DPAT, 0.25 mg/kg, i.p.) increased social behavior in a similar way to MDMA and this effect was also significantly attenuated by tocinoic acid. Taken together, these results suggest that oxytocin release, stimulated by MDMA through 5-HT1A receptors, may play a key role in the prosocial effects of MDMA and underlie some of the reinforcing effects of the drug.

 

[any major dude]

i've read a number of studies using an oxytocin nasal spray. In those it did seem to enhance or induce trust of strangers. However I've read some more recent studies that have found oxytocin to induce feelings of jealousy, gloating, etc. Just in case you thought anything neurochemistry related was simple:
The Dark Side of Oxytocin
Goody Goody Hormone Linked to Envy, Gloating

 

[PsychedelicPeptide]

MDMA is an intoxicant with strong stimulative properties. "Dealing with shyness?" It is kind of like alcohol... anything that lessens brain inhibitory signals is going to make "shy" people more pro-social. Of course MDMA and booze are vastly different in mechanism of action but the principle is the same.

You could put a "shy" person on MDMA in a room by themselves though and they would probably feel just as uninterested in socializing as usual (because they are so high [confusingly high] and the setting does not promote socialization).

Let them take a look at their strung out face in the mirror, and hell they might walk away never wanting to do MDMA around people period!

Oxytocin itself is pretty hit or miss. The problem is that it is hard to get good doses up your nose and into the right places of the brain. I've tried it on occasion but the diuretic properties are enough to deter me from using that much of it. If there is any definite mental effect from nasal oxytocin, I would say it is in the memory. I seem to remember faces very well in my head if I see them after using oxytocin. That's not to say I feel different or anything (I'm not "shy" to begin with) but that I can recall facial images in my head that I saw shortly after using the oxytocin very well in hours following use. There is science to back this up, I believe a number of studies have examined non-human primates ability to recall faces after being given oxytocin and they usually do better in these tests.

I don't know much about the effect of 8-OH-DPAT... PM where to find. ;-P

 

[ManRider]

You're dismissing mdma but I'm not really talking about what it can or can't do. That's been established pretty well by now elsewhere. I'm more interested in this oxytocin facet of it, and, more importantly, what kind of effects can be had from other compounds which also play into the oxytocin system.

8-OH-DPAT is interesting for this reason and because of the other things going on with it. From wikipedia:
"8-OH-DPAT is a research chemical of the aminotetralin chemical class which was developed in the 1980s and has been widely used to study the function of the 5-HT1A receptor. It was one of the first major 5-HT1A receptor agonists to be discovered.
Originally believed to be selective for the 5-HT1A receptor, 8-OH-DPAT was later found to act as a 5-HT7 receptor agonist and serotonin reuptake inhibitor/releasing agent as well.[1][2][3][4][5]
In animal studies, 8-OH-DPAT has been shown to possess antidepressant,[6] anxiolytic,[7] serenic,[8] anorectic,[9] antiemetic,[10] hypothermic,[11] hypotensive,[12] bradycardic,[12] hyperventilative,[13] and analgesic effects.[14]"

 

[rickolasnice]

Are there any known chemicals to bypass the 5-ht agonism and go straight onto oxytocin release?

 

[PsychedelicPeptide]

Well you're going to have to target something prior to causing oxytocin release, that is, the oxytocingeric neurons have to be stimulated to release oxytocin.

So whether that is though a molecule hitting the 5HT1A receptor, your loved one touching you or whatever else... something has to do it; there is no "way to bypass" that.

I don't think there are any other known routes though. The mechanism that social bonding (or whatever you want to call it, love, etc) causes release of oxytocin is not very well understood.

 

[rickolasnice]

^ Yeah so why couldn't you make a chemical that binds to oxytocin receptors rather than 5-ht?

 

[bben]

abilify hits with partial 5 ht1a agonism and most anti psychotics increase oxytocin through an indirect mechanism.

 

[PsychedelicPeptide]

Well the problem in using a oxytocin agonist is that oxytocin does a number of different things in the brain/body. The diuretic effect is somewhat undesirable. Overdose might cause nipple lactation.

Also there could be problems with non-specificity. A lot of times oxytocin ligands cross-react with the vasopressin receptor, which you probably don't want if your goal is stimulating the oxytocin receptor for "social effects."

So in targeting 5HT1A you could potentially get around this by just stimulating a receptor on the oxytocin neurons, but not the oxytocin receptor itself. Of course this is assuming you have a specific 5HT1A ligand to begin with.

I don't know what side effects would come with a pure 5HT1A agonist though; whether there is anything worse that could happen from simply hitting the oxytocin receptor (which at worst will make your wiener shrink unable to pee and possibly nipples lactate; women might have other issues as oxytocin can induce labor).

It is not unreasonable to think that you could have a different or even better response by stimulating the 5HT1A receptor-harboring oxytocin neurons indirectly (5HT1A receptor) versus directly (oxytocin receptor). This is because when you stimulate the 5HT1A receptor on the oxytocin-releasing neurons they will release the oxytocin as it is done naturally by the brain so it can activate the purported brain social pathways and hopefully nothing else.

This is opposed to having an oxytocin agonist travel throughout the entire brain, hitting all available oxytocin receptors in the process after you administer it. The ideal result from targeting 5HT1A then is that you may possibly get a more direct or profound effect.

Finally I am not sure what amount of oxytocingeric neurons have a 5HT1A receptor or how far oxytocin travels in the brain to hit receptors once released and these are important considerations.