The neurobiology behind morality

[alkap555]

what i'm saying is that the notion that "you are the serotonin" is bullshit because there is more to behaviour than one or two neurotransmitters (note there was no mention of violent behaviour in the man with very low serotonin function), especially when it comes to violence which is a choice that you as a human chose to engage in (which i think has more to do with cortical underarousal and mental laziness/whatever you are used to getting away with behaviour wise)

Yea you can't honestly differentiate your behavior from the underlying neural mechanisms. Sure you have control over how you act, but only to an extent, because that mechanism of control is all part of the same system. Your conscious mind is entirely dependent on brain function, it is not a distinct entity which operates independently.

By that logic, it would seem that schizophrenics are simply "mentally lazy" because they hear voices or act on delusional thoughts. At a certain point you have to accept that your brain (and the neurochemical mechanisms that govern its fxn) IS you. Obviously I am using hyperbole here, but do you see what I am trying to say?

Back to drug discussion:

Hmm only 5-HT1A? Strange... then how do we explain the extremely blunted empathogenic effect of MDAI? Perhaps 5-HT2C interfering with social behavior, the effect of which is overcome by MDMA's dopamine/norepinephrine release?

Well is MDAI an agonist at 5-HT1A, or is it simply a 5-HT releaser? I think the whole point with MDMA is that it is acts a direct 5-HT1A agonist as well as releaser of DA/NE/5-HT. And the intrinsic activity of MDMA at this receptor is likely the key, just as psilocin agonism of 5HT2A makes you trip while agonism by serotonin itself (or lisuride) does not (due to PLA2 activation vs PLC, respectively).

However, the 5HT2A is coupled to Gq, so this is kind of a diff story.

 

[atrollappears]

Well is MDAI an agonist at 5-HT1A, or is it simply a 5-HT releaser? I think the whole point with MDMA is that it is acts a direct 5-HT1A agonist as well as releaser of DA/NE/5-HT. And the intrinsic activity of MDMA at this receptor is likely the key, just as psilocin agonism of 5HT2A makes you trip while agonism by serotonin itself (or lisuride) does not (due to PLA2 activation vs PLC, respectively).

However, the 5HT2A is coupled to Gq, so this is kind of a diff story.

Oh I didn't know MDMA was a 5-HT1A agonist. So you think that it's the result of functional selectivity in 5-HT1A agonism? I had thought that only 5-HT2A and 5-HT2C were selective among serotonin receptors, but a quick google search lends credence to your theory: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697830/ Interesting...

 

[ebola?]

Wow...some of the tangential discussion here is a lot better than we usually enjoy in PandS.
Regardless of the role of specific neurotransmission, I would argue that 'the will' at no point exerts causal primacy in determining behavioral and experiential outcomes...do I choose what to desire? No, my desires guide my choices. Do I choose what thoughts will appear in my mind? No, my train of consciousness conditions what I will choose.

But I'm little invested in the game of assigning responsibility and blaming others for failure to conform to various prescriptions. I rarely find doing so useful.

ebola

 

[alkap555]

Seeing as most of the recent papers seem to agree that nobody has really investigated the mechanism of the strong empathogenic effects of MDMA, maybe this could be a good topic to start a thread (re: 5HT1ARs)? I'm pretty new here so idk if it qualifies as ADD...

 

[endotropic]

Seeing as most of the recent papers seem to agree that nobody has really investigated the mechanism of the strong empathogenic effects of MDMA, maybe this could be a good topic to start a thread (re: 5HT1ARs)? I'm pretty new here so idk if it qualifies as ADD...

So this is getting pretty far away from the central topic in this thread, but addressing 5HT1a, MDMA, and empathogenic effects in a preclinical study:

http://www.ncbi.nlm.nih.gov/pubmed/17383105
A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy").

Abstract
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-HT(1A) 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 microg, 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-HT(1A) 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-HT(1A) receptors, may play a key role in the prosocial effects of MDMA and underlie some of the reinforcing effects of the drug.

Major finding is that 5HT1a receptor seems to mediate MDMA induced adjacent lying behavior in rodents through an oxytocin dependent mechanism, and 5HT1a receptor activation alone can produce similar effects. Or as I like to tell my non-scientist friends, it causes a "rodent cuddle puddle". I always wonder why there's no more interest in direct 5HT1a agonists as recreational drugs, although it probably has something to do with the combined hypotensive and bradycardiac effects.

 

[alkap555]

^ yea thats the same paper I posted upthread.

I always wonder why there's no more interest in direct 5HT1a agonists as recreational drugs

I considered that as well...but then I remembered the azapirone class of anxiolytics (buspirone etc) that act as partial 5HT1A agonists, and their recreational value is Zero, not to mention their worthless therapeutic efficacy (IME).

Edit: Side-note--It seems that 5-MeO-DMT also has considerable affinity for the 5HT1AR:

While the prevailing view was that the activation of 5-HT2 receptors is solely responsible for hallucinogenic drug effects, these results support a role for 5-HT1A receptors in the effects of the indoleamine hallucinogen 5-MeO-DMT

http://www.springerlink.com/content/571257851858223k/


I don't have any experience with this compound, so I can't say much about it's empathogenic qualities (or lack thereof)

 

[atrollappears]

So this is getting pretty far away from the central topic in this thread, but addressing 5HT1a, MDMA, and empathogenic effects in a preclinical study:

http://www.ncbi.nlm.nih.gov/pubmed/17383105
A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy").



Major finding is that 5HT1a receptor seems to mediate MDMA induced adjacent lying behavior in rodents through an oxytocin dependent mechanism, and 5HT1a receptor activation alone can produce similar effects. Or as I like to tell my non-scientist friends, it causes a "rodent cuddle puddle". I always wonder why there's no more interest in direct 5HT1a agonists as recreational drugs, although it probably has something to do with the combined hypotensive and bradycardiac effects.

Well we knew it was mediated by 5-HT1A, the question was whether it was specific to (a) certain signal transduction pathway(s). As for why 5-HT1A agonists aren't used recreationally, I hold to my above theory on 5-HT1A autoreceptors, and the accounts of partial agonists I've heard haven't painted them as particularly intense drugs.

 

[Aetherius Rimor]

Who's flying the plane: serotonin levels, aggression and free will.

This paper really interests me. Is there a way to get access to this from somewhere that doesn't have a pay wall?

The concept of free will being non-existent due to the physical laws of the universe has been apparent to me since 9th grade AP Chem.

However the way I came to terms with the fact, was keeping mind that all actions have consequences, regardless of "who's flying the plane".

While I know we're a ways away from being able to modify behavior chemically in a predictable and planned manner to prevent aggressive behavior, it's obvious one day we may have that ability.

Then the moral/ethical dilemma is do violent offenders be forced to choose prison or forced chemical rehabilitation, do we pre-treat those with the capability for illegal violence to prevent it from ever happening... does ethics of taking away someone's "free will" even matter when the science behind that action relies on free will never having existed to begin with?

I'm far less concerned about the ethical dilemmas facing AI/Genetic Engineering than I am about the ethical dilemmas facing cognitive/neuroscience and behavioral modification.

Which will come first though, genetically engineered pre-natal cures for criminal behavior, or pharmacological corrective treatments of criminal behavior. That curiosity interests me.

 

[atrollappears]

This paper really interests me. Is there a way to get access to this from somewhere that doesn't have a pay wall?

The concept of free will being non-existent due to the physical laws of the universe has been apparent to me since 9th grade AP Chem.

However the way I came to terms with the fact, was keeping mind that all actions have consequences, regardless of "who's flying the plane".

While I know we're a ways away from being able to modify behavior chemically in a predictable and planned manner to prevent aggressive behavior, it's obvious one day we may have that ability.

Then the moral/ethical dilemma is do violent offenders be forced to choose prison or forced chemical rehabilitation, do we pre-treat those with the capability for illegal violence to prevent it from ever happening... does ethics of taking away someone's "free will" even matter when the science behind that action relies on free will never having existed to begin with?

I'm far less concerned about the ethical dilemmas facing AI/Genetic Engineering than I am about the ethical dilemmas facing cognitive/neuroscience and behavioral modification.

Which will come first though, genetically engineered pre-natal cures for criminal behavior, or pharmacological corrective treatments of criminal behavior. That curiosity interests me.

You're getting the thread back off track (though to be fair I was the one who got it off track in the first place), but I wonder why you make a distinction between your will and the physical brain. Most people seem to think that to exercise "free will" they have to be some external, arbitrary force that acts on the physical world, which, though I thought similarly at one time, I now think is a little silly. But excuse me, I just wrote 11 pages which culminated in this over the course of 4 hours, so you can say I'm currently a little involved in my ideas and apt to blabber on about them...

 

[Aetherius Rimor]

You're getting the thread back off track (though to be fair I was the one who got it off track in the first place)

; the OP posted a whole bunch of abstracts. We both were talking about one of them... not sure how we're off track with the topic XD.

We have the illusion of free will created by the abstraction of the consciousness from subconcious brain functions. This illusion of free will is what I refer to being "taken away".

 

[atrollappears]

; the OP posted a whole bunch of abstracts. We both were talking about one of them... not sure how we're off track with the topic XD.

We have the illusion of free will created by the abstraction of the consciousness from subconcious brain functions. This illusion of free will is what I refer to being "taken away".

The free will vs. determinism doesn't pertain to drug discussion, though the role of serotonin in aggression does.

I would love to discuss free will vs. determinism but I don't want to be typing paragraphs in this thread which seems to be more about serotonin, and my plane is boarding. However you should PM me. Suffice it to say that I consider our perception of causality with respect to the will an illusion, rather than the will itself. We seem to have dug ourselves into a false dichotomy in which causal laws seem to remove the ability of the will to influence our actions or even minds, and in which the concept of a will requires that it is independent of external causality. I would argue that neither is the case.

 

[sekio]

WAY-100,635 is nonselective & also a D4 dopamine agonist. Just something to spoil your fun.

 

[endotropic]

WAY-100,635 is nonselective & also a D4 dopamine agonist. Just something to spoil your fun.

That's a good point, but I don't see how D4 agonism would allow WAY-100,635 to reverse the effects of 5HT1a agonists. I don't think drug "dirtiness" takes much from the linked papers, but yes it would be nice if all pharmacological research could be replicated with different drugs with different patterns of "dirtiness" so that we could say for sure these effects are due to the primary receptor.

 

[negrogesic]

I've long found the listed side-effects of drugs such a pramipexole to be curiously hilarious. I wonder if there have been instances of hyper sexuality that have crosses genders (ie, compulsive homosexual, episodic bi-curiousity).

Conversely I know of few drugs have clearly the opposite effect, though such a drug would be interesting. Imagine a drug that causes problematic compulsive philanthropy, or idiopathic peace treaty negotiating.