Dopamine Receptors

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

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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?

Yes I stopped feeling like even more of a zombie than I did with pfs.

It helped with sleep and fatigue and when I came off I managed to be able to sleep more or less a full night not long after. But I don’t think this can be attributed to the drug. No other benefits in brain fog or sexual sides.

has anyone taken a dopamine receptor antagonist?

Guys these thread is amazing, continue with it pls! I will look for dopamine antagonist. ( I just bought L-tyrosine before reading this thread!, Would be experiencing with it a litle :smiley: )

dopamine plays a major role in PFS.

sciencedirect.com/science/ar … 9302022904

sciencedirect.com/science/ar … 0811000165

all studies ive seen point to fact that during finasteride use, dopamine levels are altered and increased. i just read in a thread somewhere else here, someone mentioned that someone who took finasteride, their libido was 10/10 and stronger than it usually is. this would make sense if dopamine is increased while on the drug. however, once the drug is stopped from being used, one would think that the dopamine would be decreased. perhaps a dopamine “tolerance” was much higher than normal and that tolerance has not been adjusted after the drug has been discontinued. similar to how some recreational drugs increase dopamine, then the user needs the drug itself in order to “feel normal” again.

fasting (long talked about on this forum for it’s positive benefits) is one of the few things that increase dopamine receptors and help to normalize this system. i believe going carb free has a similar effect (2 recoveries, Chi & IHP both went carb free for long periods of time in order to treat and effectively cure PFS)

I have been on wellbutrin XL 300mg the whole time, it is a dopamine reuptake inhibitor and non-selective, also nueropenepherine, it is an amazing antidepressant. It is the only one I know of that always works and doesn’t make you numb and increases the libido, focus, makes you lose weight, gives you energy. If you take it just make sure to take brand name only or the generic that is a white round hard pill that looks just like the brand name one, the other generics do not work right at all. Not just my opinion, the opinion of zillions of people on the net, even the FDA recalled the oval generics, but they are back out there. Often when people have bad experiences with wellbutrin XL it is because they took the bad generic. If I take the oval shaped generic I feel like shit, I highly recommend this drug.

Yeah, 9 years on finasteride, towards the last 2 years of my use, I was incredibly horny, all I talked about was sex, the closer I got to crashing the higher my libido was, really incredible libido and then of course, penis goes dead, and PFS started.

i tried the welbutrin a few year back,i wasnt on it long and it started to make me feel like shite,fucked my head up,straight in the bin…

You know I was thinking the other day, I wonder if the cure for PFS is within finasteride, interesting how some people get better for a time when going back on only to get worse. I wonder if it has something to do with the fact that none of us tapered off, we all quit cold turkey.
I am not advocating going back on the poison as it damaged me more when I went back on (not before improving my symptoms btw a bit only to get worse), just from 2 half pills, but I do wonder about that strange effect. The hell if I will be the Guinea pig for that though lol.

how does welbutrin XL work exactly? what i’m looking for is, is it increasing or decreasing dopamine and is it increasing or decreasing dopamine receptors?

or, is there another mechanism that you feel is the reason it is helping you?

I did 2 blood test this year.

One in februaray and one in June. Both came with the exact dopamine level 11ng/dl (10-110). Is that not curious?

I also feeling the less dopamine: Less motivation in general, less focus, less happines (but curiously my serotonin levels were ok and I feel in a relaxed and calm state most of the time).

Also I took L-tyrosine 1g to 2g / day for a week and I entered into a state of real focus and motivation for 4 days. The most focus that I had in a long long long (maybe never) time. I remember especially 2 days that I worked in my career project since the morning to the 1AM, only have rested for lunch and dinner for a maximun of 40min. Obviously after that I think I got a drawback and I could have had a brief psycotic-attack caused by it, in the form of paranoias and little hallucinations. Yes its documments that dopamine agonist could induce it (fortunatly).

Having not taking it since then and now started to recover motivation and focus, but nowdays Im not eating any sugars that drive my energy very low, and I try to avoid carbs unless is the morning that somedays I take some toast with butter. Maybe I should give another try with the L-tyrosine I dont know yet.

very interesting post always thought there was something wrong with my brain since stopping finasteride. Before stopping i use to enjoy smokin pot alot, nowadays it makes me anxious and i dont enjoy it anymore. only times when i can feel my high is when im in the sun(increases dopamine). Also never have libido since stopping, but when im in the sun my libido goes up a lot. maybe an idea to increase the sensitivity of dopamine receptors by following a strict circadian rhythm because melatonin and dopamine balance each other out. youtube.com/watch?v=41XIrv0btWc maybe more dark hours per day so that dopamine gets lower and sensitivity gets higher dont know if it works that way

Pff, I find the same with weed. I used to enjoy a little in my early 20s and it would relax me. Since I took Propecia I’ve tried it again a few times and each occasion it’s caused me episodes of anxiety and paranoia. I also get anxious and paranoid after drinking alcohol. I’ve read that this can happen to people anyway, and I’ve always been a more anxious person than others, but it makes me wonder how I’d be right now if I’d never taken Propecia.