Done Cocaine, Meth, Morphine 1 TIME!? Why you might want more even if you hated it.

[glitterfly]

wow Richard, thanks for that. you gave me a moment of okayness in an otherwise horrid week. i realized my post was not clearly explained and thought about deleting it until my dumbass realized i'm a newbie and can't. then i admit i got a little turned off by your post and decided to be stubborn and just leave y'all to figure it out. hehe anyway, you're probably gonna think i'm doing it again but i don't want to offer my interpretation until i've reviewed my notes and your research and am sure i know what i'm talking about this time. but i have another exam tomorrow and am already in a procrastination war zone. so hopefully i can take a break from studying tonight. next time i'll keep my big mouth shut until i can back up what i'm saying

[Forthesevenlakes]

i think mesolimbic may refer to solely the pathway between the ventral tegmentum and the nucleus accumbens, apparently alot of dopaminergic neurons there, according to wikipedia! so it probably shouldnt be read as synonymous with the limbic system. this is a good thing, because it then reinforces the hypothesis swiUS were discussing before...

Reputation Comments on this post:

oh yes... i think you're right!

[Richard_smoker]

Damn, even though you have one of the most unique names I've ever heard of--sort of like a run-on sentence inside of a word--I've decided that you are one GOOD MOTHERFUCKER!

Why don't I know anyone in REAL life who looks up stuff for me?? It's almost like you actually listen to me when I talk (well--in this case, everything I type). Nobody, and I mean NOBODY pays ANY attention to me in the real world!!


-RS

[Forthesevenlakes]

haha, i know what you mean. at several parties i was actually banned from using the phrase "mechanism of action" by one friend. everyone would be free to use substances of their choice at these, i was just disallowed from informing them loudly and drunkenly how they operated. seriously though, this discussion is good, i think we might be onto something with the intracellular signalling pathways. i should look into cAMP signalling a little more when i have the time and i bet we'd find what we're looking for with the NMDA receptors. some commonality of action or something like that.

[Richard_smoker]

Yes, from the research I've accumulated, i'm convinced that it's a combination of the NMDA antagonism and the sigma binding (formerly known as sigma opioid receptors).

we'll let the rest of the world (this community) in on our little secret in due time. Pretty cool that you even realized that about the NMDA being the most likely mechanism.

I'm pretty sure that I never told you that this was the biggest common MOA that they share. As far as intracellular thing goes, it's most likely a dumping effect of stored Calcium in the calcium stores--just like how neuromuscular junctions work.

Now if we can just get those SPECIFIC cells to increase calcium, I think we would then be onto something SERIOUS! -RS

[Forthesevenlakes]

hmm, maybe if we had some site specific delivery of a K+ channel blocker (if any exist, i cant think offhand of what would block potassium ions), it would muck with the polarization of the cell so that it would have to take up more calcium in order to mantain a certain voltage difference..that would be one way. but i have no idea how one would go about making a drug site specific..i guess if anyone did, it would already have revolutionized the pharm industry.

[Richard_smoker]

nonono.. you're on the right track! I don't know if it's the potassium channels per-se that you're wanting to much with... isn't that what botox does??? and, if you recall, botox was BAAAADD before it got aproval to paralyze muscles of wrinkling! it caused botulism!

and what about tetanus? causing tetani? if i remember correctly, that's kinda like what these poisons do, right?

[Forthesevenlakes]

crap
i think you might be right with lockjaw and botox deal..i'm going to research that later today/tonight and see what I come up with. that avenue might not be available, then. good lookin out!

[Richard_smoker]

Dude, you're one of many (ok... one of a handful) of newbie/silver people that make this site worth visiting 10, 15, sometimes even 2,000,000 times a day!

For me, at least. I can't imagine how much MORE informative this place would be if our purpose in life was to "cook" M-you-know-what...!

For me, it's cool to see the bouncing around of ideas that you couldn't even get at a fucking symposium of "experts." In short, I like it. Now don't go doing anything to get yourself banned, forsevenlakes!

Now, I think we're gonna have to find some way of including a porno thread or some other kind of sex-folder on this site!

Speaking of, what exactly is it that goes on during ORGASM? I wonder if we can bottle THAT shit up into a little drink! My guess is that it would go a LOOOOONNGG way! maybe even more addictive than the drugs we're trying to stamp-out addictions to!

Oh yeah, on another note--I know we've discussed it before (the forum), but I'm VERY interested in those nuclei surrounding the nucleus accumbens... can't recall what they're called right now, but they are, respectively the hunger and satiety centers. One is inside the other... meaning one is medial and the other is located just outside the other.

Like I said, i can't even recall what they're called, or EXACTLY where they are, but I had a professor once who had rats with electrodes placed in both sites. One rat turned into an obese FAT ASS rat, and the other wouldn't eat to save his life... NOW, if we can figure out how and if you can target those centers without putting electrodes in our brains, then we might just be onto something HUGE--kinda like viagra was/is. what do y'all think about this idea? maybe we can come up with a double-wammy... a drug that 'cures' obesity (for REAL--not like phen-fen or whatever) that also serves to MAYBE stimulate something like the happiness that comes along with good old-fashioned gluttony.

just a thought... anyone have any suggestions?? after all, it is just hypothetical / theoretical. Maybe one day it can actually be explored as a drug-target.

and--on a similar note--somewhere else, forthesevenlakes brought up another interesting idea about nicotine, satiety, and breaking the habit of smoking. This reminds me of a drug I saw one time on CNN that was being tested in France as an anti-obesity and anti-smoking drug. Want to know what kind of chemical it is?? a CANNABINOID!! yeah, that's right! they based the compound on good old THC. any thoughts? and how about this--does anyone KNOW what that drug (on CNN) is??? I would really enjoy finding out about it, and possibly checking out the structure and some research findings. Anyone, post away! this is some important stuff. no answer, suggestion, or reply is stupid! seriously, anything will be appreciated! thanks, -Dick

EDIT POST--> I just found an article, not sure if it's THE article I was searching for, but here's the reference: Appetite Regulatory Peptides: Obesity drugs and their targets: correlation of mouse knockout phenotypes with drug effects in vivo Obesity Reviews, Volume 7 Page 89 - February 2006 D. R. Powell. I'm posting the full article in another thread.
ABSTRACT: Sequencing of the human genome has yielded thousands of potential drug targets. The difficulty now is in determining which targets have real therapeutic value and should be the focus of a drug discovery effort. The available evidence suggests that knockout technology can be used prospectively to identify targets that are amenable to drug development for the treatment of a variety of diseases. This review compares the knockout phenotypes of 21 potential obesity targets with the effects of therapeutics designed for those targets on rodents and, when data were available, on humans. The phenotypes of obesity target knockouts model the effects seen when therapeutics designed for those obesity targets are delivered to rodents; of the 21 obesity targets reviewed, 16 showed a correspondence between knockout phenotype and drug effect in mice and/or rats. This suggests that, at least in terms of evaluating obesity targets, it is rare for compensatory developmental changes caused by the gene knockout to prevent detection of the relevant phenotype. In the majority of cases, the knockout phenotypes also modelled the effects seen when the relevant therapeutics were delivered to humans. Thus, it seems rational to use mouse knockout technology prospectively to identify genes that regulate body fat in vivo, and then to develop anti-obesity therapeutics by targeting the human protein products of these genes. Ultimately, the value of using this approach to identify novel targets for human anti-obesity therapies will be judged by future studies examining the anti-obesity effect, in humans, of the therapeutics that result from this approach.

[Forthesevenlakes]

it has always been mine (and my buddy SWIM's) opinion that the hypothalamus was responsible for feelings of hunger and satiety, but must re-consult some texts. but gene therapy could be an alternate means of helping to combat certain addictions or compulsive behaviors.

[Richard_smoker]

hmmmm.... hypothalamus is big. might be in there. how about mammillary bodies?? are they attached to hypothalamus...?

speculation, speculation... all i need is a damn neuro-atlas. Did I sell mine? oh yeah, um, that's a question that no one on this board knows. not even me! I'll look it up when i get off my ass.

[Forthesevenlakes]

mammilary bodies are probably near the hypothalamus, either that or they may compose part of the limbic system. i could just wikipedia it, but i'm too worn out to stare at that creepy globe-image intro screen at the moment. swim and i were just under the impression that the hypothalamus regulates, or plays a large role in regulating, alot of autonomic processes, among them the feelings of hunger/satiety and thirst. put simply, it is supposed to be the thermostat of some of the body's tendencies towards equilibriae.

[glitterfly]

hi all, i'm sorry i dipped out on this post! richard and one other person know that i basically dropped off the face of the planet for 3 weeks, or perhaps i should say that i retreated into the hell of my own mind. anyway, i'm so excited that after finals on wednesday, i can make a stop at this lovely site and continue to entertain myself and hopefully the rest of you too once again! and believe it or not i've been thinking about this post off and on for 3 weeks too, so i can't wait to clear my mind of all this "learning and memory" and "adolescent psychology" junk so i can talk about what really matters!!! drugs!!! j/k of course hahaha although i do have some ideas about learning and memory too that i'd like to see what yall think ok someone's probably gonna yell at me and say i'm in the wrong forum, sorry g'nite!

Reputation Comments on this post:

i'd love to see the learning and memory idea followed up on

[Richard_smoker]

Glitter--I'm almost CERTAIN there were others who noticed...

[glitterfly]

awww ::blushes::

[Forthesevenlakes]

hey, i noticed! glitterfly, when you get the chance you should try to tie this into some learning and memory if you have any epiphanies in that department. i'll throw in some more two cents when i get any ideas too. right now all i can think of though is how would a cannabinoid help fight nicotine addiction? i'm going to look up some stuff on it, i'll edit and post any studies or info i find.

EDIT: does anyone know if hormonal levels in the nucleus accumbens pertain to addictive behavior at all? i have found some info stating that theyre involved in mating and romantic behavior...wondering if drugs could carry similar reinforcing properties that could lead to the release of similar hormones, etc, such as oxytocin and vasopressin. heres the source that gave me the idea, hopefully someone finds this interesting enough to help me out on this:

"Reward Mechanism Involved In Addiction Likely Regulates Pair Bonds Between Monogamous Animals In their research, funded by the National Institute of Mental Health, Larry Young, PhD., associate professor of psychiatry and behavioral sciences at Emory University School of Medicine and an affiliate scientist at Yerkes National Primate Research Center; graduate student Miranda Lim; and Anne Murphy, PhD., associate professor of biology at Georgia State University, examined the distribution of two brain receptors in the ventral forebrain of monogamous prairie voles that have been previously tied to pair bond formation: oxytocin (OTR) and vasopressin V1a receptor (V1aR). Using receptor audiographic techniques, the scientists found that these receptors are confined to two of the brain's reward centers, the nucleus accumbens and the ventral pallidum. V1aR receptors, which are thought to be activated in the male vole brain during pair bond formation, were confined largely to the ventral pallidum. OTR receptors, which play a crucial role in pair bond formation in females, were found mainly in the nucleus accumbens.
The V1aR and OTR receptors did not overlap between the two brain regions, and were equally distributed in the brains of male and female voles. According to Dr. Young, the findings, coupled with the close proximity of the nucleus accumbens and ventral pallidum-- two regions with heavily interconnected structures--suggest that a common neural circuit in male and female voles regulates pair bond formation.
Past studies have found the dopamine system of the nucleus accumbens produces the rewarding and sometimes addictive effects of sex, food and drugs of abuse. Dr. Young believes the same reward pathways are likely stimulated during and following pair bond formation.
"Although the process of pair bond formation results from the activity of two different neurochemicals in separate regions of the ventral forebrain in male and female vole brains," said Young, "the OTR and V1aR systems appear to activate two separate nodes of the same reward pathway to form and reinforce pair bonds."
In another finding, the CBN researchers determined that OTR and V1aR are closely located near the nerve fibers that release oxytocin and vasopressin. Lim speculated that their proximity likely facilitates pair bond formation during mating.
CBN studies currently underway continue to examine other components of the neural circuit involved in pair bond formation.
The monogamous prairie vole, which forms lifelong pair bonds, provides an ideal animal model for studying the neural basis of social attachment. In previous studies, CBN scientists have determined:
* The genes for vasopressin and oxytocin are critical for the proper processing of social information;
* A lack of genes for vasopressin and oxytocin receptors results in a deficit in social recognition and altered anxiety in mice;
* Vasopressin and oxytocin play key roles in the formation of social attachments between animals. Increasing the amount of vasopressin receptors in the brain using gene transfer techniques can increase pair-bonding behavior in monogamous male prairie voles."


source: http://www.sciencedaily.com/releases...0121074745.htm

[glitterfly]

yay, i am loved after all. hmm emory university... never heard of that one

can't wait to contribute to this post, damnit i hate finals!!!!

[Richard_smoker]

OK. Here's what I DO know about oxytocin and the brain.

It seems that this hormone is tied into the addiction circuit in female brains. It is a smooth muscle stimulant--causing contractions in the smooth muscles of the uterus and is released in response to several different stressors including sex (female orgasm), labor (i.e. labor and delivery), and some other activities--can't remember what they are... maybe breastfeeding?

But essentially, this hormone is thought to be the 'bonding and nurturing' hormone. Like i said, it's mostly a female thing as far as i've ever been taught.

For those who are curious about this one, then perhaps you should watch the movie: Employee of the Month.

Excellent movie--i think, anyways. There's one HILARIOUS part where steve zahn describes to matt dillon how that 'love' is a creation of "chicks' brains."

This is very funny, but as far as my research could unearth, largely TRUE! It describes how that one assault of oxytocin on the female brain leads to an increasingly strong response with future exposures to the hormone... causing women to fall "in love." as far as guys falling in love--there's no explanation. However, it's still funny to hear Zahn's logic behind his statement that "Love is just an illusion created by women, man... when really all that's going on is a simple DRUG ADDICTION!" ha!

AFAIK, this part of the argument is not true, but still funny: "Oxytocin. it's a stimulant man... get's em high as a japanese kite! that's why when THEY get off, they wanna stay up and talk all night, or go feng shui the living room, dude!"

[Forthesevenlakes]

hahah lovely post richard. oxytocin also seems to be involved (along with vasopressin) in the forming of social bonds, e.g. children in orphanages seem to have lower levels of these hormones, which may reflect an inability to communicate meaningfully with others and form long-term positive bonds, as well as be properly wary of strangers. the studies on this (i'll cite the sources when i can find them, i'm going by memory here) also say that maternal love, or at least physical contact with infants is necessary for adequate levels of these hormones to be present. which could lead to an interesting conclusion that MAYBE some people use drugs as a means of indirectly raising these hormonal levels, and thus could potentially have more normalized social interactions even while sober. of course, this is a huge maybe, its just something i came up with after thinking about this data. what does everyone think?

(side note: when i was reading these papers a while back, some friends in the room kept misreading 'oxytocin' as 'oxycontin', and couldnt understand why researchers were dosing orphans with powerful opiates. ha.)

myself/swim/whoever is going to have to check out employee of the month now!