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Caffeine enhances activity of common antidepressants in forced swim test in mice

ncbi.nlm.nih.gov

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Re: Caffeine enhances activity of common antidepressants in forced swim test in mice

#21

Post by WilTimSon »

dan-robertson wrote: post #13

The methodology here is typical for testing antidepressants with animals but many people find it somewhat horrifying: First the mice are made to be depressed by exposing them to constant sounds of birds screeching and other predators. Next some are given the intervention. The level of depression is then measured by putting the mice in a container of deep water from which there is no escape, and timing how long until…

Ethical horrors aside, I'm a bit confused by their definition of depression here. I think there's a solid gap between 'constantly exposed to predators and thus feeling like there's no chance you'll survive' and 'feeling like life is just a black void of emptiness'. The latter being a very, very rudimentary description of depression that I've heard from friends.

Is there a scientist in the thread who could clear up why a mouse's will to persevere and live is equated with how depressed it is? Do mice just not perceive circumstance as well?

Re: Caffeine enhances activity of common antidepressants in forced swim test in mice

#22

Post by mattkrause »

dan-robertson wrote: post #13

The methodology here is typical for testing antidepressants with animals but many people find it somewhat horrifying: First the mice are made to be depressed by exposing them to constant sounds of birds screeching and other predators. Next some are given the intervention. The level of depression is then measured by putting the mice in a container of deep water from which there is no escape, and timing how long until…

I’m sorry but I’m having trouble believing the second part. Every university I’ve worked at has extensive training and monitoring for animal research, and there’s no way any of them would have approved what you’re describing. Screwing around with something like this could get the entire university’s federal funding cut off, and so they take compliance very seriously. Secondly, the brains are often collected as part of the experiment, and these samples would absolutely be destroyed by someone “coming up with something on the spot.”

I was so annoyed about 2nd part that I almost forgot to mention that the first part is untrue too. There’s no mention of predator sounds whatsoever in the paper. The standard forced swim test model just looks at how long the mouse actively tries to escape vs just floating too; there’s no drowning involved.

tl;dr: Lies

Re: Caffeine enhances activity of common antidepressants in forced swim test in mice

#23

Post by mattkrause »

WilTimSon wrote: post #21
dan-robertson wrote: post #13

The methodology here is typical for testing antidepressants with animals but many people find it somewhat horrifying: First the mice are made to be depressed by exposing them to constant sounds of birds screeching and other predators. Next some are given the intervention. The level of depression is then measured by putting the mice in a container of deep water from which there is no escape, and timing how long until…

Ethical horrors aside, I'm a bit confused by their definition of depression here. I think there's a solid gap between 'constantly exposed to predators and thus feeling like there's no chance you'll survive' and 'feeling like life is just a black void of emptiness'. The latter being a very, very rudimentary description of depression that I've heard from friends. Is there a scientist in the thread who could clear up wh…

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.

Re: Caffeine enhances activity of common antidepressants in forced swim test in mice

#25

Post by sjg007 »

natalyarostova wrote: post #11
seibelj wrote: post #4

My perfect day is 8 hours of caffeine, an hour at the gym, 4 hours of alcohol, SSRI for a nightcap. YMMV

While I never used alcohol, some many number of years ago my drug cocktail used to not be so dissimilar from yours. All I can say is that, for me personally, and many others, being able to eventually move off that chemical dependency has resulted in richer and healthier days. This isn't a judgement on what works for you, or a suggestion that you do some radical change. Just something to chew on in the back of your mi…

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.

Re: Caffeine enhances activity of common antidepressants in forced swim test in mice

#26

Post by WilTimSon »

mattkrause wrote: post #23
WilTimSon wrote: post #21

Earlier quoted context omitted.

Ethical horrors aside, I'm a bit confused by their definition of depression here. I think there's a solid gap between 'constantly exposed to predators and thus feeling like there's no chance you'll survive' and 'feeling like life is just a black void of emptiness'. The latter being a very, very rudimentary description of depression that I've heard from friends. Is there a scientist in the thread who could clear up wh…

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 p…

Ah, okay, that makes sense, thank you for clearing up my confusion. Basically, they're looking for the most effective substances to boost activity, which is one of the things that anti-depressants are supposed to help with.

Re: Caffeine enhances activity of common antidepressants in forced swim test in mice

#28

Post by mattkrause »

WilTimSon wrote: post #26
mattkrause wrote: post #23

Earlier quoted context omitted.

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 p…

Ah, okay, that makes sense, thank you for clearing up my confusion. Basically, they're looking for the most effective substances to boost activity, which is one of the things that anti-depressants are supposed to help with.

It’s more that substances boosting activity also help with depression: nobody really knows the causal direction, or even if there really is one.

That said, one way to botch these assays is to do something that just directly increases locomotion. They did look at that in Table 1 though.

Re: Caffeine enhances activity of common antidepressants in forced swim test in mice

#29

Post by mattkrause »

dTal wrote: post #8

They don't appear to have run a control with caffeine alone. Caffeine is a well-established athletic performance-enhancing drug in its own right. Isn't this a serious flaw with the swim-test portion of this study?

Figure 1 shows that 5,10,20,50 mg/kg caffeine has an effect on the forced-swim test, but not as strong as imipramine. Table 1 shows that the same doses of caffeine don’t make the mice more active in their cage, which might help address your concern.

Re: Caffeine enhances activity of common antidepressants in forced swim test in mice

#30

Post by andbberger »

samatman wrote: post #18
andbberger wrote: post #16

Earlier quoted context omitted.

> A second ethical issue with studies with mice is that often the unfortunate phd student tasked with dispatching the mice will not have been taught any way to do so and will have to try to come up with something on the spot. This can be quite traumatic for both parties. uhhhhhh are you sure about that?? This strikes me as a flagrant violation of policy. Animal studies are heavily regulated. In my experience, (and mi…

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.

There's a good chance I have that wrong and they use nitrogen. Like I said, I don't work in animal labs, just adjacent to them.
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