Antidepressant-like Effect Of Creatine In Mice Involves Dopaminergic Activation

[paymanz]

Antidepressant-like effect of creatine in mice involves dopaminergic activation. - PubMed - NCBI

Abstract

Creatine has been shown to play a significant role in health and disease. However, studies concerning its effect on mood are scarce. This study investigated the effect of creatine (p.o.) in the tail suspension test, a predictive test of antidepressant activity. Creatine reduced the immobility time in the tail suspension test (0.1-1000 mg/kg, male and female mice), without affecting locomotor activity. Furthermore, the involvement of the dopaminergic system in creatine-induced antidepressant-like effect in male mice in the tail suspension test was investigated. The anti-immobility effect of creatine (1 mg/kg) was prevented by the pre-treatment of mice with haloperidol (0.2 mg/kg, intraperitoneal (i.p.) route, non-selective dopamine receptor antagonist), (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390; 0.05 mg/kg, subcutaneous (s.c.) route, dopamine D₁ receptor antagonist) and sulpiride (50 mg/kg, i.p., dopamine D₂ receptor antagonist). Creatine (0.01 mg/kg, sub-effective dose) in combination with sub-effective doses of (1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine) hydrochloride (SKF38393; 0.1 mg/kg, s.c., dopamine D₁ receptor agonist), apomorphine (0.5 µg/kg, i.p., preferential dopamine D₂ receptor agonist) or bupropion (1 mg/kg, p.o., dopamine reuptake inhibitor with subtle activity on noradrenergic reuptake) reduced the immobility time in the tail suspension test as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an activation of dopamine D₁ and D₂ receptors

 

[Drareg]

Great find.
I notice the benefits of this stuff, I have it in the toolbox, for me 1 to 3 g is enough.

It definetaly has liver effects for me, I will feel nausea if I over do it. It's great though if you want to train on top of stressful jobs, the recovery seems quicker.

It would be interesting to explore the liver effects in relation to protein intake,it might indicate a low protein intake will cause the nausea when too much creatine is ingested, it comes from protein after all, vegan may have issue supplementing in this case if not careful.

 

[haidut]

Antidepressant-like effect of creatine in mice involves dopaminergic activation. - PubMed - NCBI

Abstract

Creatine has been shown to play a significant role in health and disease. However, studies concerning its effect on mood are scarce. This study investigated the effect of creatine (p.o.) in the tail suspension test, a predictive test of antidepressant activity. Creatine reduced the immobility time in the tail suspension test (0.1-1000 mg/kg, male and female mice), without affecting locomotor activity. Furthermore, the involvement of the dopaminergic system in creatine-induced antidepressant-like effect in male mice in the tail suspension test was investigated. The anti-immobility effect of creatine (1 mg/kg) was prevented by the pre-treatment of mice with haloperidol (0.2 mg/kg, intraperitoneal (i.p.) route, non-selective dopamine receptor antagonist), (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390; 0.05 mg/kg, subcutaneous (s.c.) route, dopamine D₁ receptor antagonist) and sulpiride (50 mg/kg, i.p., dopamine D₂ receptor antagonist). Creatine (0.01 mg/kg, sub-effective dose) in combination with sub-effective doses of (1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine) hydrochloride (SKF38393; 0.1 mg/kg, s.c., dopamine D₁ receptor agonist), apomorphine (0.5 µg/kg, i.p., preferential dopamine D₂ receptor agonist) or bupropion (1 mg/kg, p.o., dopamine reuptake inhibitor with subtle activity on noradrenergic reuptake) reduced the immobility time in the tail suspension test as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an activation of dopamine D₁ and D₂ receptors

This is a good find, and it is even more important considering the puny dose of creatine used, which in humans amounts to only 5mg - 7mg daily, orally. Creatine works similarly to inosine and activates the adenosine receptor, which is known to have anti-depressant effects. Sleep deprivation does the same - i.e. activates the adenosine receptor.
Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A₁ and A2A receptor activation. - PubMed - NCBI
Creatine For Depression & Bipolar Disorder: 5g Daily Supplementation

 

[Dopamine]

I was actually planning on posting this study myself but you beat me to it lol. Here are some more good ones:

Brain serotonin and dopamine modulators, perceptual responses and endurance performance during exercise in the heat following creatine supplementat... - PubMed - NCBI
"reduces plasma free tryptophan and tryptophan:tyrosine ratio"

Additive neuroprotective effects of creatine and a cyclooxygenase 2 inhibitor against dopamine depletion in the 1-methyl-4-phenyl-1,2,3,6-tetrahydr... - PubMed - NCBI
"Both rofecoxib and creatine administered alone protected against striatal dopamine depletions and loss of substantia nigra tyrosine hydroxylase immunoreactive neurons."

http://www.ncbi.nlm.nih.gov/pubmed/22080314\
"The Cr supplementation induces a significant increase in athletics performance, and it attenuated the changes observed in the urinary 8-OHdG excretion and plasma MDA. These results indicate that Cr supplementation reduced oxidative DNA damage and lipid peroxidation induced by a single bout of RE."

Creatine monohydrate in resistant depression: a preliminary study. - PubMed - NCBI
"One patient improved considerably after one week and withdrew. Both bipolar patients developed hypomania/mania. For the remaining seven patients, all scale scores significantly improved. Adverse reactions were mild and transitory."

Also read the examine page on creatine:
Creatine - Scientific Review on Usage, Dosage, Side Effects | Examine.com

@haidut new idealabs product: post workout protein supplement to facilitate recovery with casein or BCAA and creatine?

 

[paymanz]

@Dopaminergic096

thanks for add those studies , specially the first one is really cool. i add tryptophan tag.

this dopamine stuff is damn good, thx to haidut pointed to it , i wasnt giving much attention when i read about it in peat's articles.and your name

btw i hope you havent planned for other studies i want post soon just kidding.

 

[paymanz]

apparently creatine increases FFA and prolactin ,maybe because of very big dose?20g/day

and this is interesting from that study:

A number of previous classic studies have reported a significant correlation between plasma [FFA] and plasma free-[Trp] primarily due to FFA displacing Trp from its binding to albumin

 

[Dopamine]

apparently creatine increases FFA and prolactin ,maybe because of very big dose?20g/day

and this is interesting from that study:

I think it should lower prolactin and FFA. It should lower prolactin by raising dopamine, also there are some studies showing it increases bone mineral density indicative of lowered prolactin (Prolactin tends to reduce bone mineral density.) Studies show reduced lipid peroxidation which indicates lowered FFA.

A number of previous classic studies have reported a significant correlation between plasma [FFA] and plasma free-[Trp] primarily due to FFA displacing Trp from its binding to albumin

I think this study is saying that FFA raises plasma tryptophan. Creatine lowers plasma tryptophan and probaly also FFA.

 

[Parsifal]

Have you seen this thread? Creatine recommendations?

So maybe it raises prolactin?

 

[Dopamine]

Have you seen this thread? Creatine recommendations?

So maybe it raises prolactin?

I don't think so. If any thing it should lower prolactin. Also in that thread there is not enough info to say for sure that creatine was the culprit for his problems. It could just as likely have been whatever he was drinking it with... or increased exercise and stress...

 

[Parsifal]

Will try some creatine, thanks!

 

[Parsifal]

I've read that creatine increases water retention, maybe that's why some people think it increases acne (or increased DHT)? Isn't water retention mediated by prolactin/adrenaline/cortisol/serotonin/oestrogens? @haidut @Dopamine

 

[Dopamine]

I've read that creatine increases water retention, maybe that's why some people think it increases acne (or increased DHT)? Isn't water retention mediated by prolactin/adrenaline/cortisol/serotonin/oestrogens? @haidut @Dopamine

I believe Creatine more or less simply increases ATP.

“As in other cells, ATP maintains the proper water content of cells.” -Ray Peat

I think bad reactions to creatine; like acne... probaly result from impurities in manufacturing. Even though "creapure" is considered the gold standard of creatine I have heard of people having bad reactions to it then buying generic bulk creatine and they are completely fine. I think Ray has said in passing that creatine is fine if it doesn't contain impurities and that would be my current opinion as well.

I think estrogen causes water uptake by damaging cellular structure.
ATP could cause water uptake through osmosis and affecting solute distribution in the cell. Increasing solutes in a cell will increase its water volume as water moves from low solute concentration to high solute concentration in osmosis. The structure however will still be maintained. -My understanding

 

[sladerunner69]

Using creatine in the morning I was clearly feeling dopamergenic and highly energized, however half way through the day I would seem to crash and I couldnt think clearly and would just feel out of whack like everything was on the fritz. I cant take anything that prevents me from doing homework and creatine had me feeling too weird to be able to calm down and do work.

 

[ddjd]

Antidepressant-like effect of creatine in mice involves dopaminergic activation. - PubMed - NCBI

Abstract

Creatine has been shown to play a significant role in health and disease. However, studies concerning its effect on mood are scarce. This study investigated the effect of creatine (p.o.) in the tail suspension test, a predictive test of antidepressant activity. Creatine reduced the immobility time in the tail suspension test (0.1-1000 mg/kg, male and female mice), without affecting locomotor activity. Furthermore, the involvement of the dopaminergic system in creatine-induced antidepressant-like effect in male mice in the tail suspension test was investigated. The anti-immobility effect of creatine (1 mg/kg) was prevented by the pre-treatment of mice with haloperidol (0.2 mg/kg, intraperitoneal (i.p.) route, non-selective dopamine receptor antagonist), (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390; 0.05 mg/kg, subcutaneous (s.c.) route, dopamine D₁ receptor antagonist) and sulpiride (50 mg/kg, i.p., dopamine D₂ receptor antagonist). Creatine (0.01 mg/kg, sub-effective dose) in combination with sub-effective doses of (1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine) hydrochloride (SKF38393; 0.1 mg/kg, s.c., dopamine D₁ receptor agonist), apomorphine (0.5 µg/kg, i.p., preferential dopamine D₂ receptor agonist) or bupropion (1 mg/kg, p.o., dopamine reuptake inhibitor with subtle activity on noradrenergic reuptake) reduced the immobility time in the tail suspension test as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an activation of dopamine D₁ and D₂ receptors

in layman terms does this mean that creatine increases dopamine?

 

[success23]

Adenosine inhibits lipolysis. I wonder if creatine does the same ( since it activates the adenosine rceptors as stated above).

 

[TheBeard]

Adenosine inhibits lipolysis. I wonder if creatine does the same ( since it activates the adenosine rceptors as stated above).

No idea. The only thing I know is that creatine gives me kidney pain every single time I've tried it in 3g doses.