Dopamine Receptors

A lot of discussion has been had regarding the role of dopamine in the side effects we have been facing. Numerous people have claimed to have some, albeit, short-lived, results with anti-depressants and l-tyrosine. However, I theorize that a lack of dopamine may not be the cause of our issues, but rather a lack of dopamine receptors.

Consider the occasions where a PFS sufferer has taken l-tyrosine (a dopamine precursor) or Wellbutrin (a dopamine reuptake inhibitor) only to find temporary relief, and sometimes, even find themselves feeling worse than they did prior to their supplementation. I find it possible that the reason the positive effects are transient is because by increasing dopamine, PFS sufferers actually begin to further decrease their levels of dopamine receptors. An influx of dopamine, such as is seen in cocaine users, actually causes the body to respond by decreasing the number of dopamine receptors (thus creating a tolerance). In order to feel the same, one needs to increase the source of dopamine, causing more losses to the number of dopamine receptors. Similar effects have been found in obese people, where obese persons, possibly due consistently rewarding oneself with food, have less dopamine receptors than their thinner counterparts (bnl.gov/bnlweb/pubaf/pr/2001/bnlpr020101.htm).

I find further support for the dopamine receptor theory in the results seen by those who have seen improvements via exercise and/or fasting. Exercise is generally known to increase dopamine production, and consistent exercise increases the level of dopamine receptors. While people such as japanther have claimed success via fasting because fasting has “detoxification” properties, I believe that fasting may contribute to PFS healing via dopamine receptor increases. Fasting has been scientifically proven to increase the count of dopamine receptors one has (sciencedaily.com/releases/2007/10/071025091036.htm). Even marijuana (which I believe MartinM or someone from a post involving MartinM) has helped some regain libido, if only temporarily. Surprise! THC, the active ingredient in that sticky-icky some PFS sufferers have been smoking causes a release of dopamine!

Unfortunately, the most reputable list of symptoms for dopamine deficiency that I could find quickly has “The Edge Effect” as a source. Nonetheless, the symptoms of dopamine deficiency include:

Reduced ability to feel pleasure
Flat, bored, apathetic and low enthusiasm
Depressed
Low drive and motivation
Difficulty getting through a task even when interesting
Procrastinator/little urgency
Difficulty paying attention and concentrating
Slowed thinking and/or slow to learn new ideas
Crave uppers (e.g. caffeine/nicotine/diet soft drinks)
Use these to improve energy/motivation/mood
Prone to addictions (e.g. alcohol)/addictive personality
Shy/introvert
Low libido or impotence
Mentally fatigued easily and physically fatigued easily
Sleep too much and trouble getting out of bed
Put on weight easily
Family history of alcoholism/ADD/ADHD

By increasing dopamine, yes, PFS sufferers may receive some temporary resolution of symptoms. But, if PFS sufferers can increase their dopamine receptor levels, is not prolonged relief possible? Could this explain why time has been the only consistent factor with recovery? Our bodies begin to increase our dopamine receptor levels, so that more dopamine can used?

Let’s take a mathematical look at this theory…

If on a day to day basis, a PFS sufferer has 10 available dopamine receptors and 5 units of dopamine floating around, then he is at 50% utilization. However, if he takes some l-tyrosine or some Wellbutrin, he may achieve 100% efficiency by making 5 more dopamine units available. But, if the Wellbutrin/tyrosine causes dopamine levels to go past 10, then the body begins to drop dopamine receptor levels to 9, leaving the PFS sufferer with a less high level of optimal dopamine experience.

However, if a PFS sufferer increases his dopamine receptor levels via fasting or exercise from 10 to 11, then his total possible dopamine experience increases. Maybe there are some minimum thresholds (each person’s would likely be different); if a PFS sufferer reaches 13 dopamine receptors filled with dopamine, brain fog begins to subside. At 15 receptors filled, brain fog disappears. At 18 receptors filled, emotions increase. At 20 receptors, emotions restored. At 22 receptors filled, libido increases, and at 24 receptors filled, libido is restored. With this theory, a lack of dopamine receptors would mean some people can never reach 100%, even if they are filled to the brim with dopamine, because they do not have enough receptors to make use of all the available dopamine. If you have 30 units of dopamine, and only 15 receptors, well, you’re libido won’t be helped at all because you need to be filling a minimum of 22 receptors.

So - is it possible to increase the number of dopamine receptors? Yes, via exercise and fasting. Is increasing the number of dopamine receptors further/more quickly possible? Yes - through antipsychotic medications which are dopamine receptor antagonists.

Do I advocate going to your neurologist/psychiatrist and seeking out meds that will increase your dopamine receptor levels? No, because I’m not a doctor, nor a healthcare professional of any sort. Do I think this may have some promise? Yes - and it can’t have any less promise than the other methods that have been attempted.

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That sounds very interesting, you could be onto something.
I might have to start doing more exercise i think…

  1. Please cite your source claiming THC causes dopamine release. From my reading I have read the opposite, it actually blocks dopamine through a cannaboid. The cannaboid receptor system in the body was only recently discovered and has not had a lot of research done on it, however it differs from the serotonin/dopamine system.

  2. I don’t mean to hate but this list of symptoms is put out by every charlatan claiming to have the cure for ANY condition. You can literally cross reference them. These are symptoms of an antiquated education system and failing industrial society forcing active hunter-gatherers to be stationary robots, not just a dopamine deficient person. Read through them one by one. Who doesn’t feel these symptoms when they are forced to live in modern day society? The only people that don’t feel them are the ones selling you the cures, because their self-serving mugs are smiling to themselves with all the money they are making off you.

Martin -

  1. Sorry for not citing the THC item - teens.drugabuse.gov/facts/facts_mj1.php

  2. As for your second point, I would have to disagree. There are many people in modern society who do not suffer these ills. By your logic, any white collar employee would be suffering the same symptoms of PFS, thus negating any claim that PFS even exists (which I’m sure you would disagree with). Prior to finasteride use, I was the living antithesis of the symptoms I have indicated; please read my member story (Former). Additionally, if you would like to discuss societal ills at a philosophical level, I am more than willing to off the PHelp forum - I’m a bit of a philosophy junkie - but there is little use of bringing opinions about modern civilization into this discussion.

The role of dopamine in the brain cannot be understated. While our genitalia may be the sex organ, our brains make everything function. This is part of why “brain death” is now the standard for determining death, not the lack of heartbeat or respiration (or some other bodily function). Not only does dopamine act as our reward system and play a significant role in cognitive function (especially short-term and spatial memory - trouble with directions and perception anyone?), dopamine also helps to regulate the function of our pituitary gland, and thus affects the HPT axis (I can’t copy this particular link at the moment since I am at work and can’t access this .pdf). So, if we have decreased dopamine receptors, our HPTA will remain suppressed until our dopamine receptors and dopamine production are upregulated.

Martin - I do not mean to sound harsh in any way. I am just providing a hypothesis; criticism is very welcome as it forces me to drop a theory or to strengthen my support.

Thanks,

Former

Theres more to Dopamine than ‘levels’ and receptors. What about the Dopaminergic pathways and the parts of the brain that make up this system? learn.genetics.utah.edu/content/addiction/reward/pathways.html
Also, how would finasteride cause such damage and how is it possible to test for this? Any potential treatment must surely involve serious medication that should only be undertaken under the guise of a professional.

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Oscar,

Good feedback that will help to flesh out this theory. I do not have a direct mechanism for how finasteride could cause this issue (maybe related to the allopregnalone - GABA pathway?). However, I do know that dopamine regulates prolactin, so if you have low dopamine, one indicator would be high prolactin. Yet, my theory does not involve just dopamine, it involves the actual receptors. So you may have more dopamine than your receptors can actually use, and that will cause a further degradation of dopamine receptors.

A person’s level of dopamine receptors can be tested via an MRI when the dopamine binding agent IBZM is administered. This agent allows for the actual receptors to be clearly identified on an MRI. I’m not yet sure if this test will be performed by a neurologist, or only in a research setting, but I believe it may be valuable.

As for what treatment would involve, yes, treatment would likely involve supervision by a medical professional. However, for those of us who are pretty much fu**ed, trying something significant may be in the cards.

Oscar - I didn’t have a chance to look at it initially, but I think the second site that you linked may strengthen the argument for dopamine receptor issues. The site indicates dopamine plays a major role in regulating our hormones. Additionally, dopamine and serotonin work synergystically - if one is out of the balance, the other one likely is too. I believe that dopamine is the primary factor, and not serotonin, based the primary effects we are seeing (although I do also believe serotonin is affected).

So both increase dopamine levels in the brain yet one increases receptors while the other decreases them? I dont disagree with those statements but I dont think they tell the whole story either.

I agree that somehow our dopamine production/sensitivity may have been affected so I took this test about a week ago:

https://www.neurorelief.com/index.php?option=com_content&task=view&id=588

The NeuroAdrenal-Basic from this page that tests dopamine, GABA, Serotonin etc…through saliva and urine. I ordered through a local physician so Im not sure how to order from the site but it was about 250 dollars. I have no idea how accurate these things are so I might do it a few times to see if I can establish consistency, or maybe even some progress. Meanwhile, I should get the results back in a week or so…

You realize your source comes from an anti-marijuana campaign that is run by the government? There has been a lot of marijuana misinformation created by the government for the express purpose of frightening kids away from it, classifying it as a schedule 1 drug just the same as HEROIN, COCAINE, AND METHAMPHETAMINE. Overloading dopamine is the way they get kids to fear “drugs”, because kids understand what dopamine is. In fact the cannaboid system is much more complicated than this and marijuana has many active cannaboids (something like 400+). It is just beginning to be studied. So you cannot boil this down to dopamine alone, especially when researchers without government anti-drug agendas suggest the opposite. Keep in mind this is the same government that approved FINASTERIDE as a safe and legal drug for our use and got us into this mess in the first place.

Here’s a link and a graph of some properties of cannaboids (many more exist if you want further info):

forum.grasscity.com/medical-marijuana/373071-properties-cannabinoids-%5Bpic%5D.html

and another

forum.grasscity.com/medical-marijuana/645925-grannys-mmj-list-july-2010-a.html

To the second point, I have seen the same symptoms on a number of other sites. Stopthethyroidmadness has some similar ones. Not all of white collar america is suffering as bad as we are, but many are searching these things online and not broadcasting it to the world. I have a relative that works at the department of health and human services. He said one of the statistics that was brought to his attention when he joined is the high amount of self and fad internet diagnosis. And no wonder, people feel worse and most doctors are arrogant pill-pushing idiots. Just because you were the anti-thesis of these symptoms pre-fin doesn’t mean that the general population is healthy and mirroring your experience. Obesity is constantly rising. The number one calorie source in the USA comes from high-fructose corn syrup in beverages. There are a lot of people out there on “maintenance” medications which slowly wear out the body. I’ve seen a stat that says 1/5 but cannot find it. Before fin I wouldn’t mind discussing society’s ills but honestly I don’t have the energy anymore.

You’re right. Dopamine’s importance cannot be understated. I’m feeling like everything’s importance cannot be understated though. My point is how little we really know. If you find dopamine as a cure and it works for you I’m on it. However I took tyrosine and didn’t get cured. It made me feel good and a little high for a week then it stopped working too. It was very similar to when I first took magnesium. However it didn’t give me full functionality back like marijuana did. I don’t think fin just fucked our dopamine system. I think it went deeper and altered enzyme production that gives the body the ability to make, use, and store energy. It also interrupted our natural hormonal loop which got stuck on the wrong level.

Regarding exercise, I’ve reached a point where the more exercise I do the tighter my muscles get. If it is supposed to upregulate dopamine receptors, why is long term moderate exercise making me feel as if the dopamine is leaving my body?

The biggest problem we all have was a minor knowledge of the human physiology. We took this knowledge and used it not knowing the consequences. Now we’re trying to figure it out by looking at individual solutions when in fact finasteride could have blocked multiple enzymes we don’t even know about down to the cellular level leaving us with ignorance and inability to test.

Here’s a good thread on dopamine meds:

mindandmuscle.net/forum/index.php?showtopic=42580

Hey Warbler,

still new to this, but i think learning quickly. i got on the dopamine idea because of my high prolactin levels. ie. high prolactin usually accompanied by low dopamine, when its not high enough to be a prolactinoma, just the general lack of joy or feelings from anything and because my body wants to smoke cigarettes more than ever and i am happier when i have a drink or two (have stopped all together now) than i used to be from drinking. All points to low dopamine.

Anyway, Just asked Dr. Jacobs to write me a script for this test so i can get it done locally.

Wondered if you got results back and what they were etc?

thanks

I did and quite a few of the results got my attention. This test was pretty comprehensive however it did not include the inhibitory neurotransmitter taurine. The NeuroAdrenal-Expanded panel which I just ordered does. Also, it tests for dopamine and serotonin metabolites to assess receptor activity.

https://www.neurorelief.com/index.php?option=com_content&task=view&id=588

Results:
All descriptions were condensed from either my provider or the neurorelief website.

Excitatory Neurotransmitters:
All are low range or below

  1. Epinephrine: 7.5 {7-12} All units are microg/gCr unless specified
    A bit low but not notably so. Supports stress adaptation, sustained energy level, and mood.

  2. Norepinephrine: 21.8 {30-45} Low
    Helps with stress adaptation while supporting energy levels and mood again. Low Epinephrine and Norepinephrine contribute to fatigue, low stress adaptation, low mood, lack of focus/concentration, and poor memory. Low levels of Norepinephrine specifically contribute to feeling overwhelmed and subsequent anxiety.

  3. Phenylethylamine (PEA): 37.6 {30-70} nMol/gCr
    Supports mood and again, helps sustain energy levels.

  4. Histamine: 9.4 {14-24} Low
    Has the function of “pacemaker” in the brain. Regulates levels of Epinephrine and Norepinephrine.

  5. Glutamate: 15.5 {15-32} microMol/gCr
    Primary excitatory neurotransmitter responsible for most neurotransmission. Essential for thinking and memory. Low levels associated with “fuzzy thinking”, slower cognitive processing, fatigue, and inborn amino acid metabolism errors.

Inhibitory Neurotransmitters:
All are elevated save one.

  1. GABA: 7.7 {4.7-7.0} microMol/gCr High
    The infamous GABA. Major inhibitory neurotransmitter in the brain.

  2. Glycine: 1133.2 {455-980} microMol/gCr High
    Inhibitory neurotransmitter much the same as GABA but operates primarily in brain stem and spinal cord.

  3. Serotonin: 39.7 {120-185} Extremely Low
    At one third of the low end my Serotonin was by far the most striking result. Essential in maintaining balance between excitatory and inhibitory neurotransmitters which is obviously offset. Depression, fatigue, anxiety, irritability, insomnia, decreased pain tolerance, impulsivity, hypoglycemia, and insulin resistance can all be attributed to low serotonin. Sugar can temporarily raise tryptophan (serotonin precursor) crossing blood brain barrier so a craving for sweets could be sign. GABA and Glycine are elevated to compensate for low serotonin (or vice versi).

Dopamine: 152.3 {115-175}
The only neurotransmitter that is solidly in range. Dopamine gets its own category because it is both inhibitory and excitatory depending on the region of the brain it is acting. Normal urine levels may not tell the whole story and true synaptic level could be lower because low Serotonin decreases Dopamine turnover and excretion. This will hopefully be assessed along with serotonin turnover by the expanded test. I would be very surprised if my dopamine processing is completely normal due to what I percieve to be decreased reward pathway sensitivity.

Adrenal Hormones:
All elevated in response to persistent stress.

Cortisol:
Morning: 14.7 {7.0-10} ng/mL High
Midday: 8.4 {3.0-6.0} High
Evening: 4.5 {2.0-4.0} High
Night: 2.3 {<1.5} High
Stress produces an increase in HPA activity however this increase in turn creates negative feedback where Cortisol turns down the HPA axis. Persistant high cortisol is neurotoxic in the hippocampus as well as other areas of the brain. Cortisol increases neuron excitation through interference with GABA receptor. GABA and Glycine are elevated further to compensate for this. From wikipedia excessive cortisol shuts down the reproductive system and reduces Serotonin and Glutamate in the brain. When HPA finally becomes dysfunctional cortisol drops but production will be unregulated throughout the day. This is a more advanced case of adrenal fatigue than my results show. Symptoms of elevated cortisol are fatigue, decreased energy, impaired memory, insulin resistance, insomnia, anxiety, impaired concentration, restlessness, and feelings of hopelessness.

DHEA: 672.0 {250-578} pg/mL High
The most important androgen in our bodies. Dont know if there can ever be too much but high level is another indicator of adrenal stress response. My body shouldn’t need to circulate this much and this level is probably unsustainable.

I should point out that these samples were taken about two months ago. Since then I have been following my providers instructions and have been supplementing with various amino acids and supplements. Specifically those that support the adrenals and Serotonin production as well as the standard multi-Vs etc…I should have results from the advanced profile in a couple of weeks.

mindandmuscle.net/forum/index.php?showtopic=5950

The second study cited by the OP here indicates that increased GABA paradoxically increases Dopamine receptor sensitivity. This leads to me to wonder the following:

  • We are not low on dopamine, but our dopamine receptors have become desensitized due to decreased GABA levels caused by fin’s inhibition of progesterone to allopregnenalone.

  • Tyrosine may help in the short term, but its effects will fade as “supplemented” dopamine causes dopamine receptor downregulation.

  • PFS sufferers don’t lost zest for life because of dopamine, but low GABA causes anxiety, and secondarily, natural dopamine and supplemented dopamine to be ineffective.

  • Ineffective dopamine due to receptor desensitization creates longer refractory period (dopamine not as effective against prolactin, so even normal prolactin levels are problematic because dopamine cannot act properly).

  • Xyrem and other GABA modulators are may have more effect that initially thought.

  • Dopamine receptors remain desensitized unless massive GABA flooding (Xyrem, exercise (long-term)) or significant Dopamine deprivation (fasting) occurs.

I’m not saying any of this is necessarily true, but wanted to add these thoughts to our expanding knowledgebase.

Take care,

Former

Hey guys, long-time lurker, first time poster. I’ve never used Propecia, but was on TRT for 4 years, and gradually became tolerant to the effects of Testosterone, eventually ending up with complete loss of libido. This was despite all labwork returning normal (TT, Free T, E2, androgens, etc). I realize my situation may appear different from those on this board, but I am starting to believe that though the origin of my libido loss may be different, the underlying issue is the same–a mismatch of Dopamine levels and Dopamine receptors in the brain.

This is pure speculation of course, but reading this thread, a few personal observations seem to support the dopamine receptor downregulation hypothesis. I have been tolerant to the effects of supplemental Testosterone for a few years now. Not only libido, but even secondary sexual characteristics like muscle wasting, dry skin, etc. 2 years ago, I was taking 100mg/wk Testosterone injections as part of my TRT, and developed a temporary but strong coffee habit, consuming upwards of 15-20 cups a day for a month. I had a full caffeine tolerance at this point as well–I could drink as much coffee as I wanted and fall asleep right after.

When I returned home, I went cold turkey. That resulted in 4 days of the worst migraines of my life, as my dopamine levels crashed (speculation). I also stopped Testosterone replacement at this time in order to do a reset of my HPA, as per my physician. I resumed Testosterone replacement with Androderm instead of injectable, to see if another form of delivery would affect libido. Well my libido skyrocketed higher than it had been in years. This lasted a month before dropping off.

Now this could easily be theorized that the libido increase resulted from the transdermal Testosterone delivery, which increases DHT much more than injectable form. But I had been on doses of injectable Testosterone as high as 300mg/wk, which should have resulted in higher DHT, yet never increased my libido at all. I had a full tolerance to supplemental Testosterone. It was only when I went through severe caffeine withdrawals that I had a sudden surge in libido.

I speculate that the caffeine withdrawal increased Dopamine receptor levels, which re-sensitized my brain to Testosterone, restoring libido temporarily. After a month, the surge in Dopamine levels from Testosterone may have once again downregulated the amount of Dopamine receptors, bringing me back to the old state of loss of libido. Again, this is pure speculation, as I didn’t do the proper blood testing to back up my anecdote with data, but it does offer a better explanation than has ever been offered to me by any Endocrinologist or physician.

Former, have you, or do you plan on experimenting with Xyrem or any other dopamine antagonist? I thought of Seroquel as well, since it is a Dopamine antogonist but which has a few benefits, including possibly not raising Prolactin levels too much. From Wikipedia:

Seroquel also has a short half-life of only 6 hours, making it perfect to take before bed (it is commonly used as a sleeping pill). I’m hypothesizing that if someone were to take a Dopamine antagonist during sleep repeatedly, it may increase Dopamine receptor levels and resensitize the brain to Dopamine, allowing Testosterone to have the proper effect on libido. I’m not suggesting anyone be the guinea pig on this idea, but maybe there have been studies done on this effect that we could look to for further confirmation.

Any more info on this (studies etc)?

Also, if our dopamine isnt ‘working’ why arent we all depressed? Clearly some of us are depressed, but its not depression for depressions sake.

We aren’t depressed but we do have a lot of symptoms of depression. I have the anhedonia part of depression without actually feeling depressed. I think depression comes in many flavors

I’ve been thinking about this theory, and i don’t think using an anti-psychotic would help increasing dopamine receptors. People with ADHD, are supposed to have less dopamine receptors, but using an anti-psychotic has never been something considered for adhd.

Ehh - The antipsychotics don’t increase the number of receptors (to my knowledge) but the sensitivity of the current receptors.

I took Seroquel and it helped me sleep, unsurprisingly. Made me feel like a zombie though, and put on a lot of weight. Didn’t help with any PFS symptoms at all, apart from reducing fatigue due to better sleep, for which I was initially grateful. I wouldn’t recommend it to anyone.

After quitting Seroquel did you have any improvement?