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

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Mauritio

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Here's a collection of 17 dopmaniergic herbs/ supplements . I'm sure you haven't heard of some.
I find chaste berry or babchi very interesting.

 
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Dopamine causes weight loss through D1, D5 and D2 . Through different mechanisms though :
D1 and D5 = increase in adiponectin and decrease in leptin
D2 = prolactin decrease


"DAR are variably expressed at the mRNA and protein levels in adipose tissue and adipocytes during adipogenesis. ARSA activity in adipocyte increases after differentiation. DA at nM concentrations suppresses cAMP, stimulates cGMP, and activates MAPK in adipocytes. Acting via D2R-like receptors, DA and DA-S inhibit PRL gene expression and release. Acting via D1R/D5R receptors, DA suppresses leptin and stimulates adiponectin and IL-6 release."

(Dopamine receptors in human adipocytes: expression and functions - PubMed)
 

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Isn't increase in dopamine will eventually cause a downregulation/desensitization of dopamine receptors ? The same, opposite way, like antipsychotics causing an increase in D2 density, by blocking dopamine. This is a possible mechanism of paradoxical dopamine supersinsitivity syndrome and tardive dyskinesia after withdrawal. And D2 agonist like cabergoline , prevents dyskinesia. (logically by downregulating D2 eventually)



 
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golder

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Dopamine causes weight loss through D1, D5 and D2 . Through different mechanisms though :
D1 and D5 = increase in adiponectin and decrease in leptin
D2 = prolactin decrease


"DAR are variably expressed at the mRNA and protein levels in adipose tissue and adipocytes during adipogenesis. ARSA activity in adipocyte increases after differentiation. DA at nM concentrations suppresses cAMP, stimulates cGMP, and activates MAPK in adipocytes. Acting via D2R-like receptors, DA and DA-S inhibit PRL gene expression and release. Acting via D1R/D5R receptors, DA suppresses leptin and stimulates adiponectin and IL-6 release."

(Dopamine receptors in human adipocytes: expression and functions - PubMed)
Nice. What’s some of the strongest D2 agonists (as I’m also looking to lower prolactin)
 
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Mauritio

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Isn't increase in dopamine will eventually cause a downregulation/desensitization of dopamine receptors ? The same, opposite way, like antipsychotics causing an increase in D2 density, by blocking dopamine. This is a possible mechanism of paradoxical dopamine supersinsitivity syndrome and tardive dyskinesia after withdrawal. And D2 agonist like cabergoline , prevents dyskinesia. (logically by downregulating D2 eventually)



I'm not sure, but I dont think cabergoline improves dyskinesia through downregulation of D2 receptors. If that was true cabergoline would just stop working for prolactinoma after a few weeks, yet most people are on it for months, years or even decades . And it works, as long as they're on the drug.
I think it's more likely through oscillations of dopamine levels ,as the study suggests or maybe though downregulation caused by l dopa itself. Or probably something else that I just dont know about.
 
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Mauritio

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Nice. What’s some of the strongest D2 agonists (as I’m also looking to lower prolactin)
I'd say cabergoline or bromocriptine. Lisuride to a lesser extent.
But cabergoline has fibrotic side effects.
 
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D2 activation is anti-depressive :

Dopamine D2 Areceptor activation has an anti-depressant effect in androgen deficient rats .


"The results obtained here provide evidence that stimulation of D2 dopamine receptors leads to antidepressant actions in androgen-deficient male rats while blockade of D2 dopamine receptors, conversely, has a prodepressant effect."

 
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dukesbobby777

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It is right though that activation of d2 also causes downregulation. God doesn’t want us to have too much fun for prolonged periods unfortunately.
 
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Fish oil supplementation decreases dopamin D1 and D2 expression in response to amphetamines AND in the controll group that didnt receive any amphetamines.

 
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Mauritio

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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. .
D2 receptor exists in sperm as well. Implicated in sperm health and fertility. Maybe that's why selegiline and bromocriptine have been shown to help with fertility.

"We recently reported that dopamine type 2 receptors (DRD2) are present in a wide range of mammalian sperm, suggesting a role for dopaminergic signaling in events such as fertilization, capacitation, and sperm motility. In the present study, we used Western blot analysis to show that boar sperm express DRD2 and that their activation with dopamine (100 nM) has a positive effect on cell viability that can be correlated with AKT/PKB phosphorylation. Bromocriptine (100 nM) and dopamine (100 nM and 10 muM) increased tyrosine phosphorylation during the capacitation period. "

 
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Isn't increase in dopamine will eventually cause a downregulation/desensitization of dopamine receptors ? The same, opposite way, like antipsychotics causing an increase in D2 density, by blocking dopamine. This is a possible mechanism of paradoxical dopamine supersinsitivity syndrome and tardive dyskinesia after withdrawal. And D2 agonist like cabergoline , prevents dyskinesia. (logically by downregulating D2 eventually)



I know this only kind of answers your question, but I thought it was interesting and quite unique .

Selegiline increases dopamine ,while leaving the dopamine receptor sensitivity unchanged...
so that is possible.

I recently watched a podcast by andrew huberman on dopamine where he always talks about ones peaks and baseline and that you cant really influence your baseline and some people just have a higher baseline. Well, selegiline could increase your baseline while leaving your receptor sensitivity intact not leading to addiction and /or desensitization.

"The long-lasting administration of (-)deprenyl (0.25 mg/kg s.c., daily for 42 days) however, left the effects of APO unchanged, demonstrating that (-)deprenyl facilitates the dopaminergic tone in the rat brain without altering the sensitivity of DA receptors."
(Long-term administration of (-)deprenyl (selegiline), a compound which facilitates dopaminergic tone in the brain, leaves the sensitivity of dopamine receptors to apomorphine unchanged - PubMed)
 

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