What role does inflammation play in brain hormones like dopamine and leptin?

Asked on January 11, 2015
Created April 11, 2012 at 8:13 AM

I've heard a lot of talk about how important balancing our neurotransmitters is, and the ones that are mentioned are usually gaba, serotonin, acetylcholine, etc. But I hardly ever hear about dopamine. Recently I've been doing some research on it and realized I have most of the symptoms of dopamine deficiency: low energy and motivation, inability to focus, lack of excitement, food cravings, etc. I've known for a long time that I have an inflammatory bowel disorder, but I found some information showing that inflammation in the brain can destroy the neurons that produce dopamine and thus negatively affect our dopamine levels.

"Studies indicate that inflammation caused by activated glial cells and peripheral immune cells induce oxidative stress and cytokine-receptor-mediated apoptosis (programmed cell death), which could lead to dopaminergic cell death and disease progression."

So my question is, how big of a factor do you think dopamine deficiency is in depression, given what we know about how big of a role inflammation has to play in depression?

Also, I found that there's a link between dopamine and leptin: Leptin also decreases appetite in response to nutrient availability, according to Johnson's text. It is released by fat cells, indicating to the brain how much energy is being stored by the body in fat reserves in case food becomes scarce. When you put on weight, leptin levels increase. This inhibits dopaminergic neurons and decreases motivation for food because energy stores are sufficient. Conversely, when you lose weight or begin fasting, leptin levels decrease, dopaminergic neurons are activated and appetite increases to restore energy reserves.

So if obesity's primary cause is leptin resistance, and that leads to increased chronic dopamine output from those neurons, could that lead to dopamine resistance? Could this cause obese people to crave food even more since they would now need more food to experience a reward after each meal? If so, would reversing the leptin resistance be enough to reverse the dopamine resistance, and if not, what could?


on May 04, 2012
at 08:48 AM

Very interesting question but I think that focusing on leptin and dopamine(rather than inflammation as a whole) would be a mistake as the cascades of effects, both up and down stream, could be missed. The quote from the study seems like you typical pharmaceutical study to fit an already available drug therapy



on April 11, 2012
at 02:24 PM

Interesting thoughts... doesn't feeding the dopamine system lead to plain old addiction? Works with cocaine, ritalin and food, of course.

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on May 04, 2012
at 06:18 AM

Your last paragraph sums up much of the belief of the human biochemically-savvy paleo populace, as I understand it, with some qualifiers.

It is certainly the case that the leptin resistance we associate with obesity could have a role in decreased dopamine output. We have lots of the data to make those connections, they're simply scattered among studies rather than directly tested (as far as I'm aware, there are no direct tests of these hypotheses). It follows that if you could increase leptin production and receptor uptake, then theoretically you might increase dopamine production.

Part of the problem here is that dopamine is not just a central nervous system neurotransmitter ... its receptors are located in your kidneys, your bladder, your prostate, your cardiovascular system, and plenty of other places. We know that dopamine levels are decreased in major depressive disorder patients, but so also are norepinephrine and serotonin.

So is dopamine output the strict answer to your problems? Maybe, but probably not. Is it a factor? Quite possibly.

Is finding ways to increase your leptin sensitivity likely to positively impact your health and your mood? Almost certainly. Focus on doing the things you know will positively impact your physical health, and the mental health will follow. That's the takeaway point in which I believe, anyway.

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