Finasteride and/or Dopamine

General Discussion
#2

Inhibition of 5α-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation.

Cogent evidence highlights a key role of neurosteroids and androgens in schizophrenia. We recently reported that inhibition of steroid 5α-reductase (5αR), the rate-limiting enzyme in neurosteroid synthesis and androgen metabolism, elicits antipsychotic-like effects in humans and animal models, without inducing extrapyramidal side effects. To elucidate the anatomical substrates mediating these effects, we investigated the contribution of peripheral and neural structures to the behavioral effects of the 5αR inhibitor finasteride (FIN) on the prepulse inhibition (PPI) of the acoustic startle reflex (ASR), a rat paradigm that dependably simulates the sensorimotor gating impairments observed in schizophrenia and other neuropsychiatric disorders. The potential effect of drug-induced ASR modifications on PPI was excluded by measuring this index both as percent (%PPI) and absolute values (ΔPPI). In both orchidectomized and sham-operated rats, FIN prevented the %PPI deficits induced by the dopamine (DA) receptor agonists apomorphine (APO, 0.25mg/kg, SC) and d-amphetamine (AMPH, 2.5mg/kg, SC), although the latter effect was not corroborated by ΔPPI analysis. Conversely, APO-induced PPI deficits were countered by FIN infusions in the brain ventricles (10μg/1μl) and in the nucleus accumbens (NAc) shell and core (0.5μg/0.5μl/side). No significant PPI-ameliorating effect was observed following FIN injections in other brain regions, including dorsal caudate, basolateral amygdala, ventral hippocampus and medial prefrontal cortex, although a statistical trend was observed for the latter region. The efflux of DA in NAc was increased by systemic, but not intracerebral FIN administration. Taken together, these findings suggest that the role of 5αR in gating regulation is based on post-synaptic mechanisms in the NAc, and is not directly related to alterations in DA efflux in this region.
Copyright © 2011 Elsevier Ltd. All rights reserved.

#3

Inhibition of 5α-reductase attenuates behavioral effects of D1-, but not D2-like receptor agonists in C57BL/6 mice.

Converging lines of evidence point to the involvement of neurosteroids in the regulation of dopamine (DA) neurotransmission and signaling, yet the neurobiological bases of this link remain poorly understood. We previously showed that inhibition of steroid 5α-reductase (5αR), the key rate-limiting enzyme in neurosteroidogenesis, attenuates the behavioral effects of non-selective DA receptor agonists in rats, including stereotyped responses and sensorimotor gating deficits, as measured by the prepulse inhibition (PPI) of the acoustic startle reflex. Since previous findings suggested that the role of DA D(1)- and D(2)-like receptor families in behavioral regulation may exhibit broad interspecies and interstrain variations, we assessed the impact of 5αR blockade on the behavioral effects of DAergic agonists in C57BL/6 mice. The prototypical 5αR inhibitor finasteride (FIN; 25-50 mg/kg, intraperitoneally, IP) dose-dependently countered the PPI deficits and the enhancement of rearing responses induced by the full D(1)-like receptor agonist SKF-82958 (0.3 mg/kg, IP); however, FIN did not significantly affect the hyperlocomotive and startle-attenuating effects of SKF-82958. Whereas the D(2)-like receptor agonist quinpirole (QUIN; 0.5 mg/kg, IP) did not induce significant changes in PPI, the combination of this agent and FIN surprisingly produced marked gating and startle deficits. In contrast with previous data on rats, FIN did not affect the reductions of startle reflex and PPI produced by the non-selective DAergic agonist apomorphine (APO; 0.5 mg/kg, IP). These findings collectively indicate that, in C57BL/6 mice, 5αR differentially modulates the effects of D(1)- and D(2)-like receptor agonists in behavioral regulation.

#4

I’m posting an article about dopamine and sex: voices.yahoo.com/getting-high-se … 91033.html

I think its worth reading and thinking about as many of us crashed after lots of sex or masturbation after we came off the drug. I was thinking that it wasn’t just a surge in steroids but also neurotransmitters that is caused PFS. Finasteride has anti-dopaminergic effects and maybe a surge of dopamine has down-reguated dopamine receptors to an extremely low state; possibly why we have low libido and don’t feel good orgasms. In addition, many feel worse after orgasm. It could be our receptors have up-regulated a little bit since our initial crash (which is why most people don’t feel as bad as they did immediately post-crash. Furthermore every orgasm further down regulates them because of the release of dopamine and other steroids. Again, this is speculation based partially on what we know so far from the research. I’m interested in trying something that will up-regulate dopamine receptors, not just dopamine. Also, who knows what positive feedback loops there are with allopregnenalone, etc.

#5

Anyone here have Restless Leg Syndrome? I always had it. Since Awor says we’re genetically predisposed, I wonder if anyone else has this.

#6

At my crash stage, yes my feet legs would jump a lot…however this has almost disappeared along with musle twitching in my calves.

#7

I know deprenyl is being looked at since light at the end recovered and used it (we don’t know exactly what made him recover). Maybe a higher dose is necessary for other people.

Searching for substances that up-regulate dopamine or dopamine receptors.

Sulbutiamine

en.wikipedia.org/wiki/Sulbutiamine

“Although its clinical efficacy is uncertain,[3] it is the only compound used to treat asthenia that is known to selectively target the areas that are involved in the condition.[4] In addition to its use as a treatment for chronic fatigue, sulbutiamine may improve memory, reduce psycho-behavioural inhibition, and improve erectile dysfunction.”

Citicoline

en.wikipedia.org/wiki/Citicoline

Studies suggest that CDP-choline supplements increase dopamine receptor densities,[1] and suggest that CDP-choline supplementation helps prevent memory impairment resulting from poor environmental conditions.[2] Preliminary research has found that citicoline supplements help improve focus and mental energy and may possibly be useful in the treatment of attention deficit disorder.[3][4] Citicoline has also been shown to elevate ACTH independently from CRH levels and to amplify the release of other HPA axis hormones such as LH, FSH, GH and TSH in response to hypothalamic releasing factors.[5]

Thats very interesting.

Inositol supposedly up-regulates dopamine receptors, trying to find a paper that proves it. I’m wondering if the severely affected people have severely reduced dopamine receptors and thats why deprenyl doesn’t work. Light at the end was hitting the gym a week or so after his crash. I was so sick I couldn’t do anything for a month. I always suspected he was not affected as much as some of us were.

#8

I wonder if there is some positive feedback loop with neurosteroids and dopamine. Finasteride has negative effects on both of these, maybe it caused such dysregulation that some loop just broke and hasn’t been able to correct itself. I also wonder if those who recover have their dopamine receptors up-regulate.

#9

alcohol leads to an initial increase in dopamine.

#10

That may explain why some feel better after drinking a lot. I also believe there was a study showing alcohol increases neurosteroids. Dopamine and neurosteroids must be connected via some feedback loop…

Increasing dopamine will not solve the problem because that may further down regulated dopamine receptors. If this is in fact part of the problem, we want to up-regulate dopamine receptors. Fasting and refraining from sexual activity up regulates dopamine receptors. I also found some natural supplements that do so (posted above).

#11

holisticprimarycare.net/topics/t … -recovery-

I wouldn’t buy anything from them, but they have a good explanation of down regulation of dopamine via drugs.

#12
  1. my case definitely fits in this part:

  1. i feel very noticeable positive difference in my condition after night of drinking that usually lasts one day

  2. i use progesterone cream, but i feel better only when i took bromocriptine with it. I get really better- almost pre-fin, but it also doesn’t last longer than couple of hours, and it is affected by masturbation

Also, one of my mental side effects- I don’t know how many people have it- isn’t brain fog ( i had that too) but state when my brain goes on “stand by”. I am not sure how to explain it, but it is like i am frozen for a couple of seconds when some stimulus is required to get me out of there. Like when you “get in thoughts” except there are no thoughts. And it happens more frequently if i don’t sleep 7-8 hours. I am thinking whether that could be connected with dopamine… Anyway, i think this could be very important part of the puzzle. Great job man. This is definitely path to follow

#13

Thats interesting you feel better with Bromocriptine as:

“Bromocriptine is a potent agonist at dopamine D2 receptors[5] and various serotonin receptors. It also inhibits the release of glutamate, by reversing the glutamate GLT1 transporter.[6]” (en.wikipedia.org/wiki/Bromocriptine)

A doctor I saw said that body builders that have used nandrolone decanoate (cannot be broken down into DHT) and develop “decadick”, a condition very similar to ours, are prescribed Cabergoline, another dopamine D2 receptor agonist. You say you only feel temporarily better though. I’m guessing that by agonizing the D2 receptors you are activating an important dopaminergic pathway but the D2 receptors are then further down regulated, so then the effects go away. I wonder if finasteride also made the dopamine receptors hypersensitive, and thats why they are not returning to previous levels or possibly epigenetic changes have locked them at a certain level. I don’t know how neurostoids fit into this, but they must be connected some way. We know dopamine antagonizes prolactin.

#14

That “important dopaminergic pathway” actually could be- reducing my little bit over the border prolactin, so gnrh can exhibit it’s effect. That certainly happens i think. And yeah, down regulated dopamine receptors could explain why this is only temporary.

#15

There’s obviously more to the puzzle though, otherwise we wouldn’t be here now. I hope this year’s research sheds more light.

#16

I’m also a big believer in Dopamine receptors having been damaged by Finasteride.

I feel if we can some how restore balance of dopamine we may feel and up lift in mood and libido.

Anybody tried any enhancers?

I also believe in my case, the reason I no longer feel the buzz or Euphoria from alcohol is damaged and depleted dopamine receptors.

Dopamine also creates our feelings of love and affection too.

Things to increase Dopamine…

Natural:

Vegetables
Nuts
Exercise
Sleep

Supplements:

Vitamin B6
L-Phenylalanine
L-theanine
Tyrosine
Phoshatidylserine

#17

Wouldn’t raising the number of dopamine receptors further decrease dopamine? We can decrease dopamine, and that way upregulate dopamine receptors, and then slowly increase dopamine, i wonder would that help… So far, only thing i am sure will be of some worth is abstinence from all kind of things. Also, one more symptom that could confirm that dopamine plays important role in my pfs is raised cravings i feel. That is most noticeable with food, but it is same with other things like internet (news etc), porn (rare periods when i feel better) etc. But, on the other side, i wonder how much of my trouble is caused by high estrogen- raised prolactin… That’s why i hesitate to continue using bromocriptine. Ok, i am in blues kind of state, so this is only me thinking aloud…

#18

Interesting video about inositol. Doctor in this video claims that this stuff can improve not only anxiety (social anxiety really depresses me) like name of the clip implies, but also other things most probably related to dopamine, such as- to reduce cravings, eliminate brain fog, improve libido etc. Ok, some people on this forum used inositol and didn’t have much improvement, but this guy have prescribed 5g per day of it to his patients. Btw, talk about inositol starts at 4:20.

youtube.com/watch?v=UeQmGZ_5cCY

#19

So, now I don’t have any doubt- dopamine receptors are one of my main problems. Of course, i can’t be completely sure it’s the only one. Last measuring shows:
estradiol: 70,6 (34- 226)
testosteron: 32,0 (8,2- 34,8)
progesteron is in range too, i cant find the paper with numbers.

My balls shrink when i eat something. My eyes are dry. I have become socially anxious, which i haven’t been before this shit.

That last guy who recovered- cdnuts claims that fasting is the main contributor. Since inositol didn’t help me much, fasting is probably next step to take. Also, it would be helpful if anyone who tried to raise density of dopamine receptors share that experience with us.

#20

www.yourbrainonporn.com

Talks all about the dopamine link with masturbation.

Also, I do have restless leg syndrome, just in case you wanted to make it more than N=1

#21

fasting + inositol … helped me with all of my symptoms but full recovery is yet to come. I guess there are more receptors to be ‘revived’