Evidence For The Involvement Of 5-HT1A Receptor In The Acute Antidepressant-like Effect Of Creatine

[paymanz]

Evidence for the involvement of 5-HT1A receptor in the acute antidepressant-like effect of creatine in mice. - PubMed - NCBI

Creatine was previously shown to produce an antidepressant-like effect in the tail suspension test through a modulation of the dopaminergic system. In this study, the mechanisms underlying its antidepressant-like effect were further evaluated by investigating the involvement of the serotonergic system in its effect. The anti-immobility effect of creatine (1mg/kg) was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA; 100mg/kg, i.p., for 4 consecutive days, an inhibitor of serotonin (5-HT) synthesis). Creatine (0.01 mg/kg, sub-effective dose) in combination with sub-effective doses of WAY100635 (0.1mg/kg, s.c., a 5-HT1A receptor antagonist), 8-OH-DPAT (0.1mg/kg, i.p., a 5-HT1A receptor agonist) or selective serotonin reuptake inhibitors fluoxetine (5mg/kg, p.o.), paroxetine (0.1mg/kg, p.o.), citalopram (0.1mg/kg, p.o.) and sertraline (3mg/kg, p.o.) 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 interaction with 5-HT1A receptors. Of note, the present results also indicate that creatine improves the effectiveness of the selective serotonin reuptake inhibitors, a finding that may have therapeutic implications for the treatment of depressive disorders.

 

[ddjd]

Evidence for the involvement of 5-HT1A receptor in the acute antidepressant-like effect of creatine in mice. - PubMed - NCBI

Creatine was previously shown to produce an antidepressant-like effect in the tail suspension test through a modulation of the dopaminergic system. In this study, the mechanisms underlying its antidepressant-like effect were further evaluated by investigating the involvement of the serotonergic system in its effect. The anti-immobility effect of creatine (1mg/kg) was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA; 100mg/kg, i.p., for 4 consecutive days, an inhibitor of serotonin (5-HT) synthesis). Creatine (0.01 mg/kg, sub-effective dose) in combination with sub-effective doses of WAY100635 (0.1mg/kg, s.c., a 5-HT1A receptor antagonist), 8-OH-DPAT (0.1mg/kg, i.p., a 5-HT1A receptor agonist) or selective serotonin reuptake inhibitors fluoxetine (5mg/kg, p.o.), paroxetine (0.1mg/kg, p.o.), citalopram (0.1mg/kg, p.o.) and sertraline (3mg/kg, p.o.) 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 interaction with 5-HT1A receptors. Of note, the present results also indicate that creatine improves the effectiveness of the selective serotonin reuptake inhibitors, a finding that may have therapeutic implications for the treatment of depressive disorders.

So does Creatine agonise or antagonise 5ht1a?

 

[Owen B]

Creatine's effect on the body is to mimic the effect of extended exercise and endurance training and high stress: it pulls intestinal fluid away from the intestinal wall increasing the possibility of sepsis and endotoxemia. It should be avoided.

I experimented with it last summer and within a month I had a UTI.

 

[paymanz]

Creatine's effect on the body is to mimic the effect of extended exercise and endurance training and high stress: it pulls intestinal fluid away from the intestinal wall increasing the possibility of sepsis and endotoxemia. It should be avoided.

I experimented with it last summer and within a month I had a UTI.

maybe if you eat creatine powder without any liquid or food?

you mean it pulls intestinal fluid away from intestinal , into blood stream or into intestines?!

 

[paymanz]

even if what owen says be true i think taking it with some fluid or food would avoid that problem, creatine is a natural nutrient , only difference here is that its concentrated into a pure powder , so it need to be diluted.

 

[rei]

Guys, think about the methods involved, maybe this one can be filed under "highly speculative"

 

[Owen B]

maybe if you eat creatine powder without any liquid or food?

you mean it pulls intestinal fluid away from intestinal , into blood stream or into intestines?!

In studies it's called "translocation". I think that means that fluid is pulled away from the wall so that it becomes permeable. The fluid stays in the intestines but you've made your system vulnerable to sepsis. Bacteria will then get into the blood.

 

[paymanz]

thanks

 

[LeeLemonoil]

Creatine is widely used for decades, Athletes take high doses for long periods. That’s the first time I read of an UTI caused by creatine.

Also, @Owen B I don’t think the effects of creatine or rather its MoA is anything like what you wrote it mimics.

 

[Owen B]

Speculation? Maybe.

But this is the way I look at it. Google "creatine + gastrointestinal effects" and there are zounds of entries. The discussions there seem to treat all these GI symptoms as if creatine were a standard issue pharmaceutical and the symptoms were simply side effects or acceptable risks. But no one really questions them. What exactly is the cause of them?

When it comes to stress and strenuous exercise we know to associate them with GI problems.

Stress Induces Endotoxemia and Low-Grade Inflammation by Increasing Barrier Permeability
Can Endurance Sports Really Cause Harm? (May 2015) Townsend Letter, Alternative Medicine Magazine

But what else increases metabolism and causes a lot of GI problems?

Unless someone can come up with a good explanation for all the GI problems associated with creatine use, I don't think it's that much of a stretch to assume that creatine is causing the same effects in the GI tract that stress and exercise does. There's too many parallels for me. Risky business.

And it's too bad because I liked the psychological effects and the increased energy. But right from the start I experienced a horrible, queasy, sickening feeling in the gut that I tried to avoid by trying other formulations of the stuff. But I stopped and before I knew it I was in an urgent care facility with a staph infection.

 

[LeeLemonoil]

All right, that warrants consideration. I use creatine every now and then before the sport games or practices I do, no more than 5g. Increase Endurance noticeably and reliably. Never experienced bad effects GI