Caffeine enhances activity of common antidepressants in forced swim test in mice (opens in new tab)

"Table 1 shows that the same doses of caffeine don’t make the mice more active in their cage"

As a former rat owner, and a former locked-up felon, if a rat (or human) is in a cage, it tends to know and act like it's in one. Caffeine isn't going to make you suddenly more energetic in your cage unless you've got some other underlying issues, so that part of the study is instantly suspect.

It's also important to figure out the magnitude of the effect.

How much less? How does it depend on exactly how much they drank (linear, quadratic)? How much does it differ from person to person? ...?

It is obvious that it has some impact, but not at all obvious how this works in detail.

There isn't much to paraphrase, really. When my doctor was prescribing fluoxetine he offhandedly mentioned that he would start me off with a lower dose than he normally would for a person of my size and issues because I was already taking amphetamines, which meant that I wouldn't need as high a dose. The offhanded way he mentioned it gave me the impression that it was common knowledge and later another doctor also mentioned the same thing to me, but this one was not a psychiatrist but a cardiologist, farther cementing my suspicions.

When I later asked my psychiatrist about this he said that since SSRIs and amphetamines are though to complement each other (even if the science on the matter isn't really decided) the recommendation they get is to adjust the dose of SSRIs down. I'm sure the actual reason is more complex than that, maybe involving fears of serotonin syndrome, but my takeaway from it was that the effect is well known.

No idea about coffee in particular since I wasn't allowed to have any caffeine during that time.

DAT inhibitors, DA releasers and agonists are effective antidepressants in that they reduce the symptoms of depression. Drugs like Zoloft are DAT inhibitors as well as acting as SSRIs, Wellbutrin is a NET and DAT inhibitor, and MAOIs inhibit the breakdown of serotonin, DA and norepinephrine. Newer antipsychotic medications that are indicated for use as adjunct therapy for depression also have binding action at certain DA receptor sites.

The problem with dopaminergics is that they tend to be addictive, and build tolerance. Both Zoloft and Wellbutrin only inhibit a certain percentage of DAT in areas of the brain related to reward, so they aren't exactly abusable, while something like methylphenidate (which is a potent NET and DAT inhibitor) is.

Well, if you look at the results...

X cures cancer in mice

Y increases lifespan in mice

Z improves disease resistance in mice

W reverses cognitive decline in mice

The signs are all there.

There’s evidence that all of the effectiveness of antidepressants is due to the placebo effect. Contrast this with bipolar or schizophrenia where medications actually seem to benefit vs placebo.

I usually let these types of comments enable interesting discussion, but given the response and the worry that it validates someone else’s lifestyle, I must say that it was tongue-in-cheek. My perfect day does not imply my everyday. Please don’t drink alcohol for 4 hours every dear reader!

I like how this is getting flagged out - but it's 100% true - this dude is going to fry himself with practically 0% REM sleep.

I understand the parent is wrong and that correcting them was needed, but I find all this hand-wringing about ethics in animal experiments kind of absurd, since it's so obviously fundamentally unethical in the first place (or at least I know of none that aren't unethical). I suspect it's mostly just a defense mechanism to shield the human mind from the trauma of continuously inflicting mass suffering and death, much like how the Nazis established gas chambers as a less traumatic way of perpetrating genocide compared to firing squad units going village to village and potentially developing symptoms of PTSD.

In both cases, zero or less value is attributed to the lives and minds that are being assaulted and extinguished on a loop (though the value is below zero in the Nazi case and sits roughly at zero in the animal experiment case). This isn't entirely fair, since I'm sure most researchers do attempt to prevent animal suffering from being the most utterly barbaric it can be due to ethical rather than selfish reasons, but I think anything that's moderately barbaric or below is still considered justifiable in their minds and I think attempts to "soften" it do mostly fall into the selfish defense mechanism category.

I understand the great benefit to scientific progress afforded by such experiments, but there was some long-term benefit from human experimentation during WWII, as well, and there probably could've been much more future benefit if those regimes had won.

While this is standard, it shouldn't be.

Mammals sense CO2 buildup, not oxygen depletion. By smothering with CO2, the mice spend their last moments desperate to breathe and unable to.

If they were to use nitrogen instead, the mice, having no way to know they've been deprived of oxygen, would just pass out and die.

As for methods here's the list: https://animal.research.uiowa.edu/iacuc-guidelines-euthanasi...

In my work, our approved methods were isoflurane and decapitation. In some types of experiments CO2 will interfere with your result.

Probably should substitute “often” for “occasionally”. I’ve edited the comment.

I suppose there are other factors too, eg the student not thinking to say they don’t know how to kill a mouse and their advisor not thinking to ask.

That description of the experiment isn’t correct. They’re not using predator calls or anything to induce depression.

Instead, the readout is how long the mouse spends scrambling to escape vs. floating immobile in the water, usually after a “training run” that demonstrates to it that it can’t escape. You can draw some vague parallel to “coping with adversity”, but the test’s value is mostly that historically, it has predicted drugs that seem to help human patients with depression: mice receiving anti-depressants tend to spend less time immobile.