" What MicroRNA's are is basically these tiny RNA transcripts - so little peices of RNA - but they work in wonderous ways. They can basically go off and regulate longer transcripts - messenger RNA's that encode proteins, so these little MicoRNA's are master regulators of proteins.We found there's one particular MicoRNA whose increase went up in the dorsal striatum where cocaine was consumed repeatedly, and we thought that was pretty intriguing.. at the time we thought it was perhaps driving the behavior... contributing to increasing motivation to consume the drug over time.. in fact it was the complete opposite... when we overexpressed the microrna. they basically stopped taking the drug.. and the more they consumed the drug, it appeared the less they wanted it - Johnathon A Hollader, from Nature PODCAST,
This is actually pretty neat - and something I wanted to show my friend.
The idea is this microRNA is a tiny peice of RNA that somehow controls the levels of expression of other genes... because these create mRNA's.. (on their way to becoming proteins).. and these micro guys can alter them. Basically an experiment found that this microRNA.... for whatever reason...was in high expression whenever rats in high cocaine environments started to become addicted.
So the logic goes - hmm, maybe it's causing the addiction? Why not overexpress it - make them incredibly addicted? Well the opposite happened - the rats began to take less and less of the drug.. and some how or other the idea is they found the drug 'less desirable'.
Nora Volkow - my favorite person in the universe - postulated that some people have genetic profiles in the dorsal striatum of the brain from the get go (called a high d2 profile) - whenever taking some drug, the drug will cause a super intense excitement of the reward region.. so much so.. that's it's 'too high'... it's almost like a shock that's not good feeling. Other people with lower counts don't get that first excessive bang.. so they keep taking the drug. She called it 'a natural protective mechanism for some people' - that's not to say these profilers can't get addicted - it's just the first few times is more intense than others.
This might relate to the rat experiment - because it suggests that somehow or other these microRNA was acting to 'fight back' against the activation of the reward pathways from the drug. The Nature PODCAST questioned the author of the study if this same mRNA is turned in all drugs (not just cocaine) - it wasn't known yet.
Questioner: So you were looking effectively for increases in protein or genes or peices of DNA that might regulate this cocaine addiction?
Author: Yes - In our study we focused on what are called "MicroRNA's" What MicroRNA's are is basically these tiny RNA transcripts - so little peices of RNA - but they work in wonderous ways. They can basically go off and regulate longer transcripts - messenger RNA's that encode proteins, so these little MicoRNA's are master regulators of proteins if you will.. and so we thought this were really well positioned to play a role in the complex behavioral roles of additction where multiple changes happen from a drug.
Questioner: So part of the study is you had rats with access to unlimited or restricted Cocaine, and you were looking at changes in MicroRNA's if you will?
Author: Ya that's exactly what we did, and we found there's one particular MicoRNA whose increase went up in the dorsal striatum (demarko: dorsal means top, striatum comes from striated which is how the tissue looks when u look at it in a micrscope) but only in cases where there was extended access to cocaine.. where cocaine was consumed repeatedly, and we thought that was pretty intrigueing... It was MicroRNA 212, and we thought it might play a role in the pasticity involved in drug use./
Questioner: And is it aiding the process of them becoming addicted to the drug or is it preventing that?
Author: Yeah (laughs) at the time we thought it was perhaps driving the behavior... contributing to increasing motivation to consume the drug over time.. in fact it was the complete opposite. What we found was indeed this MicoRNA went up when the animals had extended access and were beginning to show addiction like behaviors. . we went and overexpressed this MicroRNA in the striatum.. it was very interesting..basically in the restricted accessed animals.. those that don't really have enough cocaine to go off and show addiction like changes.. the MicroRNA didn't do anything. .. but in animals that had extended access to the drug. .. when we overexpressed the microrna. they basically stopped taking the drug.. so overtime their intake went down and down and down. And the more they consumed the drug it appeared the less they wanted it
look what Nature's saying:
First of all, the main way people have tried to stop addiction (alcoholics anonymous, therapy whatever) has been aimed at limiting the exposure to cues of the victim.. so they don't ;get a jolt (studies suggest looking at a cue is like a mini physiological hit of the drug in the brain of addicts) from the cue.. then.. they try to give the person emotional support so the 'upregulation' of recepetors/ regrowth of nerve cell size/ etc can go back to normal. That can take a while depending on whatever the pathway was.. and there's still those new nerve cells created from the learning sessions the person had initially with the drug - hence the old 'once an addict always an addict'
This is basically a novel target for addiction. The common will obviously ask " what will the effects of increasing this mRNA in the dorsal striatum of cocaine addicts in humans be?" - and who knows. But history helps. A study done earlier that restored vision to the blind in mice - literally the process of performing the miracle Jesus did in the gospels - was met with no fanfare. Freaking curing blindness for God Sakes! The problem was it involved injecting stem cells (I believe) in the retina, but what's most intriguing is these mice were BORN unable to see from the get go. Anyway, I've read stories where the blind-to-see-transition for 'humans' has started to come into effect - so here's hopin for this.