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Stress Leads To Lower Dopamine And More Drinking

Discussion in 'Scientific Studies' started by haidut, Nov 11, 2016.

  1. haidut

    haidut Member

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    The study was really on alcohol consumption what affects it. It has been known since the 1960s that people drink more when under stress but to this day mainstream medicine denies that there is a causative link between stress and substance abuse. I posted a few studies showing that "addicts" have higher levels of cortisol and that lowering cortisol or opposing its effects usually terminates the "addictive" behavior.
    This study adds more evidence to that idea. It found that stress lowers the dopaminergic effects of alcohol and that led to more drinking in the animals. Giving the animals cortisol antagonists abolilshed the increase in drinking and even stopped the self-administration of alcohol (i.e. animal model of addiction) completely. As I posted in other threads, pregnenolone is known to reduce both alcohol preference and to opposes its intoxication effects. The mechanism is likely the ability of pregnenolone to block the CRH "receptors" in the brain and thus stop the stress reaction.
    Perhaps most interestingly, the inhibition by stress of dopamine response to ethanol was blocked by acetazolamide, which suggests a role of metabolism once again. While the study did not explicitly mention the role of CO2 in protecting dopamine levels from negative effects of
    stress, no other plausible mechanism of acetazolamide is known. A very effective OTC carbonic anhydrase inhibitor is thiamine (vitamin B1). This effect of thiamine probably explains why thiamine is a common treatment for acute alcohol intoxication and in some countries is also given to reduce alcohol cravings. Furthermore, I posted a study showing thiamine lowered cortisol in humans. This means thiamine may be able to provide the benefits of BOTH acetazolamide and the glucocorticoid antagonist RU486.


    http://www.cell.com/neuron/fulltext/S0896-6273(16)30618-3
    "...Stress is a well-known risk factor for subsequent alcohol abuse, but the neural mechanisms underlying interactions between stress and alcohol remain largely unknown. Addictive drug reinforcement and stress signaling involve common neural circuitry, including the mesolimbic dopamine system. We demonstrate in rodents that pre-exposure to stress attenuates alcohol-induced dopamine responses and increases alcohol self-administration. The blunted dopamine signaling resulted from ethanol-induced excitation of GABA neurons in the ventral tegmental area. Excitation of GABA neurons was mediated by GABAA receptor activation and involved stress-induced functional downregulation of the K+, Cl− cotransporter, KCC2. Blocking stress hormone receptors, enhancing KCC2 function, or preventing excitatory GABA signaling by alternative methods all prevented the attenuated alcohol-induced dopamine response and prevented the increased alcohol self-administration. These results demonstrate that stress alters the neural and behavioral responses to alcohol through a neuroendocrine signal that shifts inhibitory GABA transmission toward excitation."

    "...Given that stress promoted excitatory GABA input onto VTA GABA neurons, we tested whether this phenomenon mediated the stress-induced alterations in alcohol's actions. Based on the results of our repetitive stimulation studies (Figures 5D and 5E), we bath applied acetazolamide to prevent changes in GABA and DA neuron firing to ethanol observed after stress. We found that upon application of ethanol, there was no longer a difference in GABA and DA neuron firing rates between control and stressed groups (Figures 6A and 6B, black and red traces compared to the dotted red lines representing stress without acetazolamide).
     
  2. Velve921

    Velve921 Member

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    The part where you discuss Pregnenolone decreasing the effects of alcohol intoxification makes so much sense. In the last couple years since fixing my metabolism I never get blacked out or have hangovers. Even when I get drunk I've never gotten to a point where I feel out of control or do not feel present; before following Peat I could easily go into a black out mode. I never get hungover either; I can wake up tired but never debilitated in bed. I am sure the whole diet and supplementation makes the largest difference, but I know when I go out drinking I will sip sugar, caffiene, and ingest thyroid hormone throughout the evening. Before bed time I will generally do thyroid hormone, ice cream, OJ, salt, and Gerolsteiner mineral water.

    Great stuff Haidut!
     
  3. Sucrates

    Sucrates Member

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  4. OP
    haidut

    haidut Member

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    Serotonin most certainly plays a role but this study actually found acetazolamide (see above edited post), which raises CO2 levels, to be directly beneficial. Acetazolamide does a number of things, including lowering plasma cortisol and serotonin, so it probably has multiple benefits. Given the role of CO2 as a biomarker of proper metabolism I think this underscores once again the link between stress, deranged metabolism, and mental disorders like "addiction". And they tell you in school that only weak people drink to excess...
     
  5. DaveFoster

    DaveFoster Member

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    @haidut

    Interesting that you noted acetazolamide. I've been taking famotidine, 20 mg twice per day, which functions as a CA inhibitor as per the study you posted, haidut IIRC.

    My concentration, ability to focus, and general well-being is greatly increased. Its synergizing greatly with topical DHEA and pregnenolone in Pansterone.
     
  6. natedawggh

    natedawggh Member

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    Yeah it do!
     
  7. tomisonbottom

    tomisonbottom Member

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    I'm confused about dopamine. It always seems to be recommended as something good and something to increase, but when I google dopamine and stress, it seems to by part of the sympathetic nervous system; i.e. a stress hormone. If we are trying to lower stress, do we really want to increase dopamine? Is it's value solely in the fact that it opposes serotonin?
     
  8. OP
    haidut

    haidut Member

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    Estrogen and cortisol are also part of the cholesterol-pregnenolone-progesterone pathway. Dopamine is itself usually benign but it can have toxicity like anything else. The catecholamines are metabolites of dopamine so the issue would usualy not be dopamine but abnormally fast degradation of it to adrenaline/noradrenaline. That is why drugs like MAO-B are used - to inhibit dopamine breakdown. Look up selegiline, it is even used for lifespan extension. So, the dopamine dominance is preferable to serotonin dominance but like anything else in excess it can cause issues but the issue usually not with dopamine but with its metabolites, usually formed by reaction with iron.
     
  9. Regina

    Regina Member

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    Haidut, could you point me to where I can learn more about the dopamine reaction with iron?
     
  10. OP
    haidut

    haidut Member

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    Ray talks about it in his recent interviews. Here is also one link from NathanK. If you Google search the forum for "dopamine iron" you will probably find more links.
    Fluorescent light kills dopamine in the brain
    "...The study used bright (fluorescent) light on surgically blinded mice and found it oxidized dopamine at a much faster rate ultimately impairing dopaminergic neurons in the substantia nigra. The wavelength penetrated the brain where dopamine interacted with iron to auto-oxidize (essentially giving them Parkinsons). In contrast, near IR is neuroprotective of those neurons."
     
  11. Regina

    Regina Member

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    Thank you Haidut. More connecting the dots.
    We spend a lot of time indoors in Chicago. And my beautiful dojo has a sea of fluorescent lights overhead. I feel them as soon as I step onto the mat. I become kind of like a fainting goat dosed with speed.
    Hmm. Well, I'll do what I can about iron stores....
    Thank you.
     
  12. Regina

    Regina Member

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    So, even in wikipedia this "broken heart syndrome",
    Takotsubo cardiomyopathy - Wikipedia
    "Scientists believe one reason is that estrogen causes the release of catecholamine and glucocorticoid in response to mental stress."
    estrogen is involved. (?) Would you think aspirin and vitamin E (and maybe succinic acid) could improve this stress condition?
     
  13. REOSIRENS

    REOSIRENS Member

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    That's why people under quite a lot of stress craves for the high dopamine gives... Adrenaline from racing...sex... Betting ... Partying... Seeing new things(places... new clothes ...experiences... one night stand partners...)

    And one form to stop going to extremities is by numbing stress with Gaba (alcohol...or things that increase blood sugar levels niacinamide cyproheptadine thiamine magnesium...things that are useful to stop addiction)
     
  14. OP
    haidut

    haidut Member

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    Absolutely, in the absence of estrogen the stress response stops as soon as the stressor is removed. So, anything that opposes estrogen should help including vitamin E, aspirin, antihistamine drugs, anticholinergic drugs, progesterone, etc.
     
  15. Regina

    Regina Member

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    :thumbsup:Thx Haidut.
     
  16. Regina

    Regina Member

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    Haidut, Attached is the results of bloodwork on 5/25 detailing my iron/copper status, lipid et al. I had the tests done as follow-up to very high NE on blood catecholamines. My low TSH and super low "iron" numbers scared the bejeezus out of my Doctor. I would be very grateful for any thoughts you might have on my results. Thank you!!
     

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  17. OP
    haidut

    haidut Member

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    Ferritin and iron saturation are indeed low. Are you taking anything that lowers iron? Aspirin, vitamin E, etc? Do you have heavy menstrual bleeding? Are you eating liver/meat at least once weekly? Are you taking thyroid for TSH to be that low?
     
  18. Regina

    Regina Member

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    Thank you haidut. I was taking 2 succinic acid pills per day for about two wks. I stopped 3 (I think) days before the test. As well, yes I do usually take aspirin and E daily.
    I have permanently stopped menstruating several months ago. (barely any for about a year).
    Off and on, I will take either tyronene or tyromix in tiny doses.
    I had been feeling great recently. After a few succinic acid days, I felt good training. I FINALLY feel like my body is handling the increase sugar/fructose and that metabolism stabilized.

    I have not gone back to succinic acid or any thyroid. But still do estroban every morning and often some aspirin before training.
    I sure don't feel anemic. (trained like a beast last night)

    Mr Doc is highly alarmed, saying I'm hyperthyroid with occult blood in GI!!!!!

    I don't think so. But really appreciate your thoughts so much.

    I just counted the succinic acid capsules that are left in the 120 ct bottle. 2 capsules = 500mg. There are 51 capsules left. So, I took 2 per day for 34 days (time flies).

    Also on day of test: BP 120/72; Pulse 70; Temp 98.3
     
  19. Regina

    Regina Member

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    Take that low iron!
     

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  20. OP
    haidut

    haidut Member

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    The low ferritin may have more to do with your high adrenaline/noradrenaline results you posted before. Has the doctor seen those results?
     
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