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 is obvious that it has some impact, but not at all obvious how this works in detail.
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.
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.
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.
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 mind if the day ever comes where you get sick of it all.
Thumbs up on the exercise though.
For example, I myself am about 65 kg and I can easily chug 5-6 pints of beer and be only slightly sleepy the next day.
But I know for sure that my alcohol habits are not sustainable because the next day my stomach (bowels, etc) is having a hurricane. Not sure what would happen if I did this every day (but I did that when I was 22).
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 the mouse gives up swimming. The mice are not left to drown but are fished out and killed in a presumably more-humane way (chronically depressed mice are not otherwise useful).
A second ethical issue with studies with mice is that occasionally 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.
If only I were being facetious.
boclinic.org/diseases-conditions/depression/in-depth/ssris/art-20044825
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
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.
uhhhhhh are you sure about that?? This strikes me as a flagrant violation of policy. Animal studies are heavily regulated.
In my experience, (and mind you I've only ever worked adjacent to animal labs, not directly in them) there is always a canister of CO2 and a euthanization chamber on standby in experiments where there is a risk of injuring the mice.
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.
In my work, our approved methods were isoflurane and decapitation. In some types of experiments CO2 will interfere with your result.
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.
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?
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.
Here are the accepted methods for "dispatching the mice": https://animal.research.uiowa.edu/iacuc-guidelines-euthanasi...
You can decide whether you think this is satisfying to you, or you can consult the bioethicists that helped develop these protocols.
If any PhD is making up ways to kill their animals, then they either didn’t pay attention or work for a crappy lab.
Regardless, that could certainly explain the caffeine-only part, but it’s harder to square with the caffeine*anti-depressant effect.
[0] Yes, like the rats! It's a real institute (National Institute for Mental Health).
Jenner, however, is an engineer like the rest of us.
Basically, alcohol is uncontroversially terrible for sleep quality.
A lot of SSRIs have the expected mechanism of action of disrupting your executive function. This is usually explained as making you more likely to act. The other is disrupting the linking and creation of long term memories, especially negative ones. You can find research evaluating SSRIs and antidepressents looking for these things. Maybe it's not bad, but long term memory and good executive function are the main components of IQ.
In the above case the stimulants were originally prescribed I think to counteract a loss of focus, they might be worse off without them.
Personally I lost a year and a half to Lexapro. It made me happy (or made me think I was) but completely removed any motivation I had to do anything. In my observations this is typical, and a concern I expressed to the doctors involved. People I've known turned into shells of themselves who never left the house.
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.
I don’t know any researcher that likes sacrificing animals though every single one is painfully aware of the moral weight. They also go out of their way to minimize suffering, for ethical reasons, for selfish reasons, and even to improve the quality of the data. The reason I jumped down the parent's throat is because it reinforces the mistaken idea that scientists are okay with “moderately barbaric” things and indifferent to suffering. We aren’t!
And what’s the alternative to animal research? Computational modeling isn’t there yet and in vitro experiments have pretty stark limitations too. In any case, both would need animal data to determine if they’re correct. Waiting for another Nazi regime[0], as you proposed(!), doesn’t seem like a viable—-or ethical—-option.
[0] Incidentally, I have read that most of that “data” was scientifically useless, not just because of its moral provenance, but also because the stuff that was done was more akin to torture than controlled research.
Whether or not one of those two arguments is compelling to you is another story.
My impression is that animal work is literally never the cheap or fast option. It's slow, it's labor-intensive, and it's expensive, while career incentives favor doing things that are quick and cheap.
It's certainly true that someone could have run a version of this study where patients with depression were "prescribed" different doses of caffeine and asked to fill out rating scales to quantify its effects on their symptoms. This experiment could reveal its effect on symptoms, the headline of this article, but it wouldn't suffice for understanding the pharmacological mechanisms (see Table 4). I don't think there are PET ligands available for any of those metabolites, and even if there were (and ignoring the animal work needed to develop them), injecting people with radioactive tracers also raises ethical questions.
I never said they were okay with it. Merely that they're still participating in it regularly, and need a way to justify it.