Inflammation, motivation and dopamine

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Will Brink

Member
There's a fascinating connection between inflammation, dopamine, and motivation:

"Why do we feel listless when we are recovering from an illness? The answer is, apparently, that low-grade chronic inflammation interferes with the dopaminergic signaling system in the brain that motivates us to do things.

This was reported in a new paper published in the journal Trends in Cognitive Sciences.


The research carried out at Emory University explains the links between the reduced release of dopamine in the brain, the motivation to do things, and the presence of an inflammatory reaction in the body. It also presents the possibility that this is part of the body’s effort to optimize its energy expenditure during such inflammatory episodes, citing evidence gathered during their study.


The authors also published an experimental framework based on computational tools, devised to test the theory.


The underlying hypothesis is that the body needs more energy to heal a wound or overcome an infection, for instance, both of which are associated with low-grade inflammation. To ensure that energy is available, the brain uses an adaptive technique to reduce the natural drive to perform other tasks which could potentially drain away the energy needed for healing. This is essentially a recalibration of the specialized reward neurons in the motivation center of the brain, so that ordinary tasks no longer feel like they’re worth doing.'

Cont:

Chronic inflammation removes motivation by reducing dopamine in the brain
 
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DragonBits

Well-Known Member
There's a fascinating connection between inflammation, dopamine, and motivation:

"Why do we feel listless when we are recovering from an illness? The answer is, apparently, that low-grade chronic inflammation interferes with the dopaminergic signaling system in the brain that motivates us to do things.

This was reported in a new paper published in the journal Trends in Cognitive Sciences.


The research carried out at Emory University explains the links between the reduced release of dopamine in the brain, the motivation to do things, and the presence of an inflammatory reaction in the body. It also presents the possibility that this is part of the body’s effort to optimize its energy expenditure during such inflammatory episodes, citing evidence gathered during their study.


The authors also published an experimental framework based on computational tools, devised to test the theory.


The underlying hypothesis is that the body needs more energy to heal a wound or overcome an infection, for instance, both of which are associated with low-grade inflammation. To ensure that energy is available, the brain uses an adaptive technique to reduce the natural drive to perform other tasks which could potentially drain away the energy needed for healing. This is essentially a recalibration of the specialized reward neurons in the motivation center of the brain, so that ordinary tasks no longer feel like they’re worth doing.'

Cont:

Chronic inflammation removes motivation by reducing dopamine in the brain

I think it's interesting that inflammation can make you less motivated.

They fail to state what level of immune cytokines is low level inflammation or which immune cytokines that are taking about. That is typical in these articles, they say low level X is a problem, but never state what low levels actually are.

  • Interleukin-1 beta (IL-1β) - One of the key mediators of the inflammatory response to physical stress. Higher levels are associated with anxiety, panic disorders, and cardiovascular risk.
Cytokine Panel | Blood Test | Life Extension

So it would imply that too much physical exercise would result in this listless behavior, which we sort of intuit from experience that too much exercise is counter productive.

One can test these immune cytokines as a group, (Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6) Interleukin-8 (IL-8), Tumor necrosis factor alpha (TNF-α)) that is kind of expensive at one place I see $399.00. And what to about it once you get results.

I doubt most of us will have problems with most of these, they are associated with cancers, and Hepatitis C, rheumatoid arthritis, etc.

Only Interleukin-1 beta (IL-1β) is associated with stress.

I also wonder if you test c-reactive protein, does a low hs c-reactive mean that elevated cytokines are unlikely? If HS-crp is 2.5, should you test cytokines? 2.5 is still considered a healthy level, but the lower the better for hs-crp.

BTW, I think inflammation is very important but in general isn't a popular excel male topic.
 

davidrn

Active Member
A topic that concerns me the most, even above T levels, is inflammation.. I have RA, and use both LDN and a (RA stronger) strain of CBD with less THC as a tincture at bedtime. Having had CRP levels in the 80's, I understand why testing helps monitor inflammation. For the past few years, still on the current regimen, I have kept my CRP below 1, for the prior 3 tests it was actually 0.5. I also use fish oil to help keep it low, but believe the LDN helps the most with increasing Dopamine (receptors) , LDN doesn't increase Dopamine, it shuts down the receptors (during sleep for a few hours) and the body responds by creating more receptors, or making them more available. I have read here and on LDN forums that many folks are using LDN for life extending benefits. It has no known side effects, (weird dreams first week for some) and is low cost, simple to make up a dose yourself, instead of buying thru a compounding pharmacy. \
Those with RA have a group of ten tests that creates a score, and is retested yearly, and includes interleukin, TNA alpha, Leptin, etc
 

Will Brink

Member
I think it's interesting that inflammation can make you less motivated.

They fail to state what level of immune cytokines is low level inflammation or which immune cytokines that are taking about. That is typical in these articles, they say low level X is a problem, but never state what low levels actually are.

It's a summary article for non scientists. Probably have to read the actual paper for the granular details on that info. I have not read the paper myself:

Treadway M. T. et al., (2019). Can’t or Won’t? Immunometabolic Constraints on Dopaminergic Drive. Trends in Cognitive Sciences.

I'm assuming they're the "usual suspects" of inflammation, but it's also not that simple: what's happening in the brain often not well reflected in basic tests looking at levels in serum, etc.

  • Interleukin-1 beta (IL-1β) - One of the key mediators of the inflammatory response to physical stress. Higher levels are associated with anxiety, panic disorders, and cardiovascular risk.
Cytokine Panel | Blood Test | Life Extension

So it would imply that too much physical exercise would result in this listless behavior, which we sort of intuit from experience that too much exercise is counter productive.

One can test these immune cytokines as a group, (Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6) Interleukin-8 (IL-8), Tumor necrosis factor alpha (TNF-α)) that is kind of expensive at one place I see $399.00. And what to about it once you get results.

I doubt most of us will have problems with most of these, they are associated with cancers, and Hepatitis C, rheumatoid arthritis, etc.

Only Interleukin-1 beta (IL-1β) is associated with stress.

I also wonder if you test c-reactive protein, does a low hs c-reactive mean that elevated cytokines are unlikely? If HS-crp is 2.5, should you test cytokines? 2.5 is still considered a healthy level, but the lower the better for hs-crp.

BTW, I think inflammation is very important but in general isn't a popular excel male topic.

Well, lack of motivation seems a very common topic on EM, especially when TRT does not seem to improve it for some, and this may be a key area to address. It's very speculative stuff, but inflammation is a factor, or a cause, in a long list of stuff best avoided, so another topic to be aware of for people looking for possible answers on EM. It may also be why some anti inflammatory foods and supps, such as fish oil, are associated with improved mood and such.
 

jonro

New Member
I would be interested in trying LDN, but where can you get it? I don't know much about naltrexone, but wouldn't you have to be an addict or alcoholic to get a doctor to prescribe it?
 

Kaes

Member
Easy to get. Works for digestive issues, energy, inflammation, even libido to a degree. Caused me a little weight gain, though.
 

davidrn

Active Member
Finding an MD who actually knows what LDN is the biggest issue. If you live in a state where they have Naturopaths that could speed up the process. Myself, I have a functional PCP and my Rheumatologist is also a functional MD, so, she encouraged me to continue taking LDN (which is an immune stimulator) and I was taking RA drugs to be immunsuppressed. She said, even though it is counter intuitive, she had patients that had been taking both for some time, and thought it helped. If you check out some of the LDN forums, they can help with finding an MD who is knowledgeable.
 

davidrn

Active Member
I didn't look at shipping costs, but at less than $2.50 a tab, it is worth a short term experiment to see if it helps. I would assume a 6 month trial is about the minimum. The starting dosage is usually 1.5ml at bedtime. The easiest way to "make" it is to take one 50mg tab, dropped into a 500ml bottle of water, shake, and take dosage. 10ml = 1mg, so a starting dosage would be 15ml (3 teaspoons) = 1.5mg. Buying it thru a compounding pharmacy really increases the total costs. The first months doses would only cost one tab, 15ml x 30 doses =450ml (best to increase by 0.5 mg) , the max dose is 4.5mg. Only common side effect starting is the first week, may effect dreams, not bad, just more vivid.
 

Cataceous

Super Moderator
If 50 mg of the drug is dissolved in 50 mL of water then that's 1 mg per mL, meaning 3/4 mL of liquid to get 3/4 mg of drug. If you go for 200 mL of water then it's 3 mL per 3/4 mg of drug.
 
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