Low Dopamine D2 receptor density leads to obesity and insulin resistance , D2 agonism may treat

[Mauritio]

These studies show that the Dopmine D2 receptors are strongly involved in obesity and insulin resistance .

1. (Brain dopamine and obesity - PubMed)

"Striatal dopamine D2 receptor availability was significantly lower in the ten obese individuals (2.47 [SD 0.36]) than in controls (2.99 [0.41]; p < or = 0.0075). In the obese individuals body mass index (BMI) correlated negatively with the measures of D2 receptors (r=0.84; p < or = 0.002); the individuals with the lowest D2 values had the largest BMI. By contrast, neither whole brain nor striatal metabolism differed between obese individuals and controls, indicating that striatal reductions in D2 receptors were not due to a systematic reduction in radiotracer .



2. (Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors - PubMed)

"We had previously documented a reduction in dopamine D2 receptors in morbidly obese subjects."

"In obese subjects striatal D2 receptor availability was lower than controls and was positively correlated with metabolism in dorsolateral prefrontal, medial orbitofrontal, anterior cingulate gyrus and somatosensory cortices."

"The associations between striatal D2 receptors and prefrontal metabolism in obese subjects suggest that decreases in striatal D2 receptors could contribute to overeating via their modulation of striatal prefrontal pathways, which participate in inhibitory control and salience attribution. "

3. Last but not least, there is this book by lyle Macdonald on bromocriptine ,which explains the mechanism of D2 agonism and increased insulin /leptin sensitivity very well .
(Awesome Bromocriptine Book By Lyle Mcdonald)

This study has the same conclusion as the book : "...diminished insulin sensitivity is related to less endogenous dopamine at dopamine D2/3 receptor in the ventral striatum."
(Reduced insulin sensitivity is related to less endogenous dopamine at D2/3 receptors in the ventral striatum of healthy nonobese humans - PubMed)

So dopamin D2 agonism seems important to keep insulin sensitivity , lower /adequate appetite and in generel a lower body weight.
Besides that this the MoA through which bromocriptine lowers prolactin , and increases insulin and leptin sensitivity .

Btw, cyproheptadine is a D2 receptor antagonist . Many people claim the antagonism isn't significant , but if the antagonism isn't enough to matter, then how come cypro has increased appetite and weight gain as side effects .
The exact things that D2 antagonism causes!

I do think it's a great anti-stress tool ,but this shouldn't be ignored/ kept in mind when taking it. .

 

[jaype]

Interesting, Do you know of any other substances that are D2 agonists? I know Uridine is involved in the D1 receptor. I've read that vitamin D3 and Creatine help in this regard

 

[Kvothe]

Btw, cyproheptadine is a D2 receptor antagonist . Many people claim the antagonism isn't significant , but if the antagonism isn't enough to matter, then how come cypro has increased appetite and weight gain as side effects .
The exact things that D2 antagonism causes!

Because it lowers the activity of serotonine, which is one of the main regulators of appetite. It supresses hunger by lowering the energy production of the body. That's why some serotonergic drugs are used as anti-obesity drugs. In the long-run, serotonin will probably cause obesity but before the body's setpoint has been set so low it often leads to weight loss due to lack of appetite. Saying that cyproheptadine has dangerous anti-dopamine effects because it increases hunger is like saying that SSRIs are a wonderful thing because they decrease hunger and can lead to quick weight loss.

Behav Brain Res 2015 Jan 15;277:14-31.
Serotonin controlling feeding and satiety

Jörg-Peter Voigt 1 , Heidrun Fink 2

Abstract​

Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and 'true' satiation and satiety. Currently, 5-HT1B, 5-HT2C and 5-HT6 receptors have been identified to mediate serotonergic satiety in different ways. The recently approved anti-obesity drug lorcaserin is a 5-HT2C receptor agonist. In brain, both hypothalamic (arcuate nucleus, paraventricular nucleus) and extrahypothalamic sites (parabrachial nucleus, nucleus of the solitary tract) have been identified to mediate the serotonergic control of satiety. Serotonin interacts within the hypothalamus with endogenous orexigenic (Neuropeptide Y/Agouti related protein) and anorectic (α-melanocyte stimulating hormone) peptides. In the nucleus of the solitary tract serotonin integrates peripheral satiety signals. Here, the 5-HT3, but possibly also the 5-HT2C receptor play a role. It has been found that 5-HT acts in concert with such peripheral signals as cholecystokinin and leptin. Despite the recent advances of our knowledge, many of the complex interactions between 5-HT and other satiety factors are not fully understood yet. Further progress in research will also advance the development of new serotonergic anti-obesity drugs.

"The multitude of 5-HT receptor families and 5-HT receptor subtypes in mammals (Barnes [11-13] and the complex serotonergic innervation of the mammalian brain [14] can possibly explain why 5-HT is involved in so many behaviours [15]. Evidence for an involvement of serotonin in food intake in men accumulated primarily during the 1960s. Thus appetite stimulating properties of the antihistaminergic/antiserotonergic drug cyproheptadine in humans and animals have been reported in the 1960s [16, 17]. During the same decade, fenfluramine (Ponderax) has been introduced as an anti-obesity drug, demonstrating significant weight loss in obese patients [18]. Fenfluramine is an amphetamine analogue and amphetamines’ weight reducing effects are known since the 1930s [19-21]. In contrast to the original amphetamines, fenfluramine had no addictive properties allowing its usage as an appetite suppressant on a wider scale. Brain lesions and pharmacological experiments using 5-HT antagonists [22-26] revealed that the hypophagic effect of fenfluramine is indeed based on its serotonergic properties."

Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity - PubMed

The pivotal role of 5-HT in the control of appetite was formally proposed nearly 30 years ago. In particular endogenous hypothalamic 5-HT has been implicated in the processes of within meal satiation and the end state of post meal satiety. Of the numerous 5-HT receptor subtypes currently...

pubmed.ncbi.nlm.nih.gov

"Specifically, 5-HT drugs reduce appetite prior to and after the consumption of fixed caloric loads, and reduce pre meal appetite and caloric intake at ad libitum meals. Clinically significant weight loss over a year or more can be produced by both d-fenfluramine and sibutramine treatment, but apparently not by the SSRI fluoxetine. Treatment with the preferential 5-HT(2C) receptor agonist mCPP and the serotonin precursor 5-HTP has also been shown to produce weight loss in the obese."

 

[Mauritio]

Interesting, Do you know of any other substances that are D2 agonists? I know Uridine is involved in the D1 receptor. I've read that vitamin D3 and Creatine help in this regard

LSD and phenylpiracetam IIRC .
Here's a list .

Dopamine receptor D2 - Wikipedia

en.m.wikipedia.org

 

[Mauritio]

Because it lowers the activity of serotonine, which is one of the main regulators of appetite. It supresses hunger by lowering the energy production of the body. That's why some serotonergic drugs are used as anti-obesity drugs. In the long-run, serotonin will probably cause obesity but before the body's setpoint has been set so low it often leads to weight loss due to lack of appetite. Saying that cyproheptadine has dangerous anti-dopamine effects because it increases hunger is like saying that SSRIs are a wonderful thing because they decrease hunger and can lead to quick weight loss.

Behav Brain Res 2015 Jan 15;277:14-31.
Serotonin controlling feeding and satiety

Jörg-Peter Voigt 1 , Heidrun Fink 2

Abstract​

Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and 'true' satiation and satiety. Currently, 5-HT1B, 5-HT2C and 5-HT6 receptors have been identified to mediate serotonergic satiety in different ways. The recently approved anti-obesity drug lorcaserin is a 5-HT2C receptor agonist. In brain, both hypothalamic (arcuate nucleus, paraventricular nucleus) and extrahypothalamic sites (parabrachial nucleus, nucleus of the solitary tract) have been identified to mediate the serotonergic control of satiety. Serotonin interacts within the hypothalamus with endogenous orexigenic (Neuropeptide Y/Agouti related protein) and anorectic (α-melanocyte stimulating hormone) peptides. In the nucleus of the solitary tract serotonin integrates peripheral satiety signals. Here, the 5-HT3, but possibly also the 5-HT2C receptor play a role. It has been found that 5-HT acts in concert with such peripheral signals as cholecystokinin and leptin. Despite the recent advances of our knowledge, many of the complex interactions between 5-HT and other satiety factors are not fully understood yet. Further progress in research will also advance the development of new serotonergic anti-obesity drugs.

"The multitude of 5-HT receptor families and 5-HT receptor subtypes in mammals (Barnes [11-13] and the complex serotonergic innervation of the mammalian brain [14] can possibly explain why 5-HT is involved in so many behaviours [15]. Evidence for an involvement of serotonin in food intake in men accumulated primarily during the 1960s. Thus appetite stimulating properties of the antihistaminergic/antiserotonergic drug cyproheptadine in humans and animals have been reported in the 1960s [16, 17]. During the same decade, fenfluramine (Ponderax) has been introduced as an anti-obesity drug, demonstrating significant weight loss in obese patients [18]. Fenfluramine is an amphetamine analogue and amphetamines’ weight reducing effects are known since the 1930s [19-21]. In contrast to the original amphetamines, fenfluramine had no addictive properties allowing its usage as an appetite suppressant on a wider scale. Brain lesions and pharmacological experiments using 5-HT antagonists [22-26] revealed that the hypophagic effect of fenfluramine is indeed based on its serotonergic properties."

Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity - PubMed

The pivotal role of 5-HT in the control of appetite was formally proposed nearly 30 years ago. In particular endogenous hypothalamic 5-HT has been implicated in the processes of within meal satiation and the end state of post meal satiety. Of the numerous 5-HT receptor subtypes currently...

pubmed.ncbi.nlm.nih.gov

"Specifically, 5-HT drugs reduce appetite prior to and after the consumption of fixed caloric loads, and reduce pre meal appetite and caloric intake at ad libitum meals. Clinically significant weight loss over a year or more can be produced by both d-fenfluramine and sibutramine treatment, but apparently not by the SSRI fluoxetine. Treatment with the preferential 5-HT(2C) receptor agonist mCPP and the serotonin precursor 5-HTP has also been shown to produce weight loss in the obese."

Wow that conclusion of you is complete bs . I never said those effects are dangerous. I literally said it's only something to keep in mind .

 

[Kvothe]

Wow that conclusion of you is complete bs . I never said those effects are dangerous. I literally said it's only something to keep in mind .

Of course you insinuated that the anti-dopamine effects are dangerous by pointing out that the antagonism to dopamine was significant and that the increased appetite following cyproheptadine administration is analogous to the reduced dopamine activity in obese people. Your serotonine seems to be elevated. Maybe you should consider some cypro.

 

[Razvan]

Of course you insinuated that the anti-dopamine effects are dangerous by pointing out that the antagonism to dopamine was significant and that the increased appetite following cyproheptadine administration is analogous to the reduced dopamine activity in obese people. Your serotonine seems to be elevated. Maybe you should consider some cypro.

Nice dude, you can't live without cypro,don't you? Learn to use your brain more without substances.

 

[Kvothe]

Nice dude, you can't live without cypro,don't you? Learn to use your brain more without substances.

I don't take any cypro. I am not sure how an organ like the brain can be used without substances.

 

[yashi]

So how would one increase D2 receptor availability without specific drugs?

 

[Korven]

So how would one increase D2 receptor availability without specific drugs?

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it ...

www.ncbi.nlm.nih.gov

 

[Mauritio]

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it ...

www.ncbi.nlm.nih.gov

Red light /sunlight as well .

 

[Korven]

Red light /sunlight as well .

For sure... nothing better than drinking coffee and being out in the sun.

I think thiamine could also be helpful for boosting dopamine as it's been shown to improve PD symptoms: An open-label pilot study with high-dose thiamine in Parkinson's disease

We suppose that the improvement of the energetic metabolism of the survivors neurons in the substantia nigra, due to the high doses of thiamine, could lead to an increase of synthesis and release of the endogenous dopamine, to an increase of activity of the thiamine-dependent enzymes, or to a better utilization of the exogenous levodopa (Jiménez-Jiménez et al., 1999; Lu’o’ng and Nguyên, 2012; Costantini et al. 2015).

 

[LeeLemonoil]

B2 and B6

 

[Gustav3Y]

While I have said this before, but back when Cypro syrup ( Peritol brand for example) was being prescribed by doctors to children often for getting them to be less active and sleep more and often to kids which had no appetite and where anorexic.
Definitely the doses weren't small as far as I see, so there is an argument there.
At least this is what was the case 20-30years ago with several doctors I know, so they are not that young doctors.
So there is actual use of Cypro for getting some people to be less active, sleep more and get fatter, how and by which reasoning several doctors ended up I do not know, definitely online sources had nothing to do with some generations.

It is interesting is how many common substances are D2 antagonists, H2 antagonists for reducing stomach acid, proton pump inhibitors for reducing stomach acid, antihistamines like Cinnarizine, up to metoclopramide.

 

[Mauritio]

For sure... nothing better than drinking coffee and being out in the sun.

I think thiamine could also be helpful for boosting dopamine as it's been shown to improve PD symptoms: An open-label pilot study with high-dose thiamine in Parkinson's disease

This is an insanely detailed article with some nuggets in it .

256+ Ways To Increase Dopamine Naturally (Supplements And Genetics) — MyBioHack | Unlock Your Genetics

Dopamine is extremely important for everyday function and plays a much larger role in the body than just bonding, motivation, cognition, emotion, well-being, and movement. Unfortunately, our environment today is very good at manipulating and hijacking our dopamine system. In this post we

mybiohack.com

Some interesting ones :

-High salt diet (Effect of salt intake and potassium supplementation on urinary renalase and serum dopamine levels in Chinese adults - PubMed) , maybe through decrease in serotonin caused by high salt ?

- D2/D3 receptors correlate with social status!
(Brain Dopamine Receptor Density Correlates with Social Status)
Jordan Peterson's lobster theory =wrong ?
He said serotonin correlates to high social status in animals .

- Pregnenolone sulfate increases dopamine (The neurosteroid pregnenolone sulphate increases dopamine release and the dopaminergic response to morphine in the rat nucleus accumbens - PubMed)


- piper longum protects dopaminergic neurons agent endotoxin
(Alkaloids from piper longum protect dopaminergic neurons against inflammation-mediated damage induced by intranigral injection of lipopolysaccharide - PubMed)


- Dopamine increases oxytocin strongly.
(Normal male sexual function: emphasis on orgasm and ejaculation)

 

[Gustav3Y]

Is Jordan a reliable source of information? We know he had hair implants and denies it, even if it obvious if you see his pictures before and after,
The reason I say this is because if you see some videos he claims his hair got back because he fixed metabolic issues, while his own rule is to always tell the truth.

 

[Gustav3Y]

I had to find the video where Jordan talk about serotonin and lobsters.
The video starts where he talks about it.

 

[Quelsatron]

Is Jordan a reliable source of information? We know he had hair implants and denies it, even if it obvious if you see his pictures before and after,
The reason I say this is because if you see some videos he claims his hair got back because he fixed metabolic issues, while his own rule is to always tell the truth.

He knows about as much about biology as anyone, so no.

 

[Mauritio]

Is Jordan a reliable source of information? We know he had hair implants and denies it, even if it obvious if you see his pictures before and after,
The reason I say this is because if you see some videos he claims his hair got back because he fixed metabolic issues, while his own rule is to always tell the truth.

No. I was more amused about how wrong he was because I remember an interview where he asked the interviewer:
" do you really want to challenge me on my neuro chemistry ? " the answer should have been : " yes because it's completely upside down " lol

 

[GorillaHead]

No. I was more amused about how wrong he was because I remember an interview where he asked the interviewer:
" do you really want to challenge me on my neuro chemistry ? " the answer should have been : " yes because it's completely upside down " lol

Its because he follows dogma. Also this thread is awesome