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Offlinemorrowasted
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Researchers discover novel potential target for drug addiction treatment * 1
    #26452202 - 01/25/20 04:34 PM (4 years, 4 days ago)

https://www.eurekalert.org/pub_releases/2020-01/uomm-rdn011520.php?fbclid=IwAR000ffTV9f7TBgqbNLlh_J3gBI8Ip9DET618Titf3NPqzEX-XU1SerFCmM

Quote:

MINNEAPOLIS, MN- January 15, 2020 - New University of Minnesota Medical School research discovers a novel potential target for treating drug addiction through "the hidden stars of the brain."

Dopamine is one of the major reward molecules of the brain and contributes to learning, memory and motivated behaviors. Disruption of dopamine is associated with addiction-related disorders, such as amphetamine substance use and abuse.

A new study published in Neuron suggests that targeting astrocyte calcium signaling could decrease the behavioral effects of amphetamine. The study was co-led by Michelle Corkrum, PhD, a third-year medical student in the Medical Scientist Training Program (MD/PhD) at the University of Minnesota Medical School, and Ana Covelo, PhD, in the lab of Alfonso Araque, PhD, and in collaboration with Mark Thomas, PhD.

Named for their star-shape, Corkrum describes astrocytes as "the hidden stars of the brain." Astrocytes have traditionally been considered "support cells" of the brain and ignored in terms of actively contributing to brain function. This study shows that astrocytes do contribute to information processing and to how organisms think and function in this world.

Corkrum and colleagues found that astrocytes respond to dopamine with increases in calcium in the nucleus accumbens, one of the major reward centers in the brain. This increase in calcium was related to the release of ATP/adenosine to modulate neural activity in the nucleus accumbens. Then, they looked specifically at amphetamine because it is known to increase dopamine and psychomotor activity in organisms. They found that astrocytes respond to amphetamine with increases in calcium, and if astrocyte activity is ablated, the behavioral effect of amphetamine decreases in a mouse model.

"These findings suggest that astrocytes contribute to amphetamine signaling, dopamine signaling and overall reward signaling in the brain," Corkrum said. "Because of this, astrocytes are a potentially novel cell type that can be specifically targeted to develop efficacious therapies for diseases with dysregulated dopamine."

Corkrum attributes the success of this study to the collaborative nature of the University of Minnesota and throughout the graduate program in neuroscience. "We were able to integrate the phenomenal resources that the U of M offers to conduct state-of-the-art research and work with numerous different core facilities, which played key roles in this study," Corkrum said.

Corkrum plans to continue this research and explore what happens with repeated exposures, withdrawal and reinstatement of amphetamine and how the stage of addiction or disease state could affect the need to increase or decrease the activity of astrocytes.




Dopamine-Evoked Synaptic Regulation in the Nucleus Accumbens Requires Astrocyte Activity


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InvisibleCognitive_Shift
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Re: Researchers discover novel potential target for drug addiction treatment [Re: morrowasted] * 1
    #26452408 - 01/25/20 06:47 PM (4 years, 4 days ago)

Very cool but only theoretical at this point.


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Re: Researchers discover novel potential target for drug addiction treatment [Re: Cognitive_Shift]
    #26452992 - 01/26/20 06:25 AM (4 years, 3 days ago)

Quote:

Cognitive_Shift said:
Very cool but only theoretical at this point.




exactly, come to me when you have facts.


and miss you Cog


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Offlinemorrowasted
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Re: Researchers discover novel potential target for drug addiction treatment [Re: SnowDaze]
    #26453018 - 01/26/20 06:50 AM (4 years, 3 days ago)

Y'all are being unfair.



These are facts.

The research is exciting even if no drugs are ever developed. Just understanding the function is astrocytes is interesting.


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InvisibleHolybullshit
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Re: Researchers discover novel potential target for drug addiction treatment [Re: morrowasted]
    #26453137 - 01/26/20 08:26 AM (4 years, 3 days ago)

So calcium channel blockers? Not really new or all that effective in man...I mean, perhaps it elucidates how/why VOCCs are involved in addiction/dependence, which is new, and may allow development of new drug candidates that more specifically and potently target astrocytes that could be more efficacious; but I won't hold my breath.

Quote:

The research is exciting even if no drugs are ever developed. Just understanding the function is astrocytes is interesting.




It's definitely interesting, and the implications concerning how astrocytes function in the brain are important, especially compared to our previous view of them, possibly creating new opportunities for future drug development concerning mental health in general, but for addiction...well, they've been finding "potential new targets for drug addiction treatment" in the brain on a very regular basis for decades now; and nothing substantial has ever come from any of them.

Of course, a lot of that has to do with a lack of interest/funding to pursue said research and drug development...even then, the effects are so "weak" in man that I'd be surprised if anything could ever garner FDA approval, let alone consumer interest. I have no doubt that drugs affecting many of said targets could be very useful in combating addiction, and could have been developed with existing knowledge many years ago, but none of them are/will be a magic bullet, and unfortunately in this society that means they will never find use.


Edited by Holybullshit (01/26/20 08:41 AM)


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Offlinemorrowasted
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Re: Researchers discover novel potential target for drug addiction treatment [Re: Holybullshit] * 1
    #26453175 - 01/26/20 09:04 AM (4 years, 3 days ago)

Not calcium channel blockers. This would be an upstream mechanism working In the cns


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InvisibleHolybullshit
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Re: Researchers discover novel potential target for drug addiction treatment [Re: morrowasted]
    #26453204 - 01/26/20 09:24 AM (4 years, 3 days ago)

VOCCs are what regulate intracellular Ca++ in astrocytes, and it is already known that L-type CCBs inhibit the (re)activity of astrocytes.


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Re: Researchers discover novel potential target for drug addiction treatment [Re: morrowasted] * 1
    #26453323 - 01/26/20 10:58 AM (4 years, 3 days ago)

I think it's unfortunate that researchers still believe that dopamine is some kind of "reward circuit" or involved in "reward signaling" or something. There's just a huge fundamental misunderstanding about the role of dopamine in the brain in science currently. Dopamine is not inherently rewarding, nor is it involved in the reward signaling of the brain directly. It just tells the brain "do this thing again." It's more like a repetition center, and is more involved in energy and motivation than in reward.

When you have a boring repetitive job and you've been working on it for a while, and you find you're in a groove doing it automatically, that's dopamine. It's not rewarding. It is associated with the reward centers of the brain no doubt, because the brain wants you to do something rewarding again. But it's about repetition and motivation, not reward. Dopamine just tells the brain "do this thing again." So naturally it's associated with addiction, but it doesn't have to do with reward. Dopamine is also involved in focus, so naturally it's activated when something pleasurable happens because your brain is focusing on the pleasure.

This is something that bugs me with virtually every article I read that mentions dopamine. They always act like it's the main way the brain receives reward when it isn't actually rewarding at all.


Edited by nooneman (01/26/20 11:02 AM)


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Offlinemorrowasted
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Re: Researchers discover novel potential target for drug addiction treatment [Re: Holybullshit]
    #26453351 - 01/26/20 11:17 AM (4 years, 3 days ago)

Quote:

Holybullshit said:
VOCCs are what regulate intracellular Ca++ in astrocytes, and it is already known that L-type CCBs inhibit the (re)activity of astrocytes.



I wonder if this is why I do not find alcohol or stimulants to have recreational value since starting gabapentin. If that is the case, it has been fairly effective for me. Then again, lots of heroin users abuse gabapentin


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Offlinemorrowasted
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Re: Researchers discover novel potential target for drug addiction treatment [Re: nooneman]
    #26453362 - 01/26/20 11:24 AM (4 years, 3 days ago)

Quote:

nooneman said:
I think it's unfortunate that researchers still believe that dopamine is some kind of "reward circuit" or involved in "reward signaling" or something. There's just a huge fundamental misunderstanding about the role of dopamine in the brain in science currently. Dopamine is not inherently rewarding, nor is it involved in the reward signaling of the brain directly. It just tells the brain "do this thing again." It's more like a repetition center, and is more involved in energy and motivation than in reward.

When you have a boring repetitive job and you've been working on it for a while, and you find you're in a groove doing it automatically, that's dopamine. It's not rewarding. It is associated with the reward centers of the brain no doubt, because the brain wants you to do something rewarding again. But it's about repetition and motivation, not reward. Dopamine just tells the brain "do this thing again." So naturally it's associated with addiction, but it doesn't have to do with reward. Dopamine is also involved in focus, so naturally it's activated when something pleasurable happens because your brain is focusing on the pleasure.

This is something that bugs me with virtually every article I read that mentions dopamine. They always act like it's the main way the brain receives reward when it isn't actually rewarding at all.




These views are not mutually exclusive. Addiction represents a kind of pathological learning. It is activation of the NA that produces the reward. It just so happens that these neurons are activated by dopamine, and that the dopamine neurons are activated by drugs of abuse in the VTA.


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InvisibleHolybullshit
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Re: Researchers discover novel potential target for drug addiction treatment [Re: morrowasted]
    #26454100 - 01/26/20 07:34 PM (4 years, 3 days ago)

Quote:

morrowasted said:
Quote:

Holybullshit said:
VOCCs are what regulate intracellular Ca++ in astrocytes, and it is already known that L-type CCBs inhibit the (re)activity of astrocytes.



I wonder if this is why I do not find alcohol or stimulants to have recreational value since starting gabapentin. If that is the case, it has been fairly effective for me. Then again, lots of heroin users abuse gabapentin




That's the thing, these compounds are most likely to only help people not compulsively take addictive substances when their use is already light. For people deep into addiction they won't do jack. And that makes it both very hard to test their effectiveness and even harder to come up with a treatment protocol which could gain FDA approval and be worth bringing to market.


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InvisibleHolybullshit
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Re: Researchers discover novel potential target for drug addiction treatment [Re: nooneman]
    #26454111 - 01/26/20 07:42 PM (4 years, 3 days ago)

Quote:

nooneman said:
This is something that bugs me with virtually every article I read that mentions dopamine. They always act like it's the main way the brain receives reward when it isn't actually rewarding at all.




I understand your sentiment and don't totally disagree...but for the sake of expediency and often clarity(you'd have to explain this to a layman every single time you talked about dopamine and reward) it is easier to use such language when discussing these subjects.

After all, functionally there isn't much difference as generally the goal is to stop reward-seeking behavior...which the dopaminergic system is most central to. It's not so important which neurons are responsible for the sensation, all that matters is what parts of the brain are responsible for the compulsion to repeat it.

Sure, dopamine is responsible for all sorts of stuff...most of which has nothing to do with addiction. But it is responsible for the reinforcing effects of reward, which is really the heart of the matter.


Edited by Holybullshit (01/26/20 07:44 PM)


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InvisibleHolybullshit
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Re: Researchers discover novel potential target for drug addiction treatment [Re: morrowasted]
    #26477616 - 02/09/20 08:35 PM (3 years, 11 months ago)

As a life long poly-substance user and former heroin addict, I know the struggle.

And drugs like this would probably be useful in staving off relapse, not stopping active addiction, in some individuals...but it would be like throwing darts, and they will never see FDA approval as the cost to get them that far would be too prohibitive, the experiments very complicated, and while I personally believe any degree of efficacy would be worth the work and be worth making them available to drug addicts...the pharma oligarchy and FDA won't agree.


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