Pharmacology - What can we learn from animal studies?

[endlessness]

So when reading the Shulgin Index, I saw that he mentions a lot of different publications regarding animal tests. Researchers test things like ´catatonic response in cats´, ´head twitching in mouse´, and other such things.

Not to get into a ´should animal studies be done´ argument, I´m just wondering about the studies that have been already performed, what kind of clues can we get from them?

For example, does head twitching in animals usually equate to stimulant properties in humans, etc .... ?

Also, what about LD50´s, are the mg/kg amounts in animal LD50s usually similar to human LD50s, in the cases that we do know?

Thanks

 

[benzyme]

rats don't puke.
just sayin'.

 

[endlessness]

And how´s that relevant? That overdoses can´t be aborted through vomiting and hence LD50s for humans will probably be higher (in cases of oral dosaging) ? or..... ? Not sure what other way that is relevant?

 

[benzyme]

what part of 'just sayin' don't you get?
it's a visceral response, something not neurologically hardwired in rats.
the rat CNS isn't quite the same as a human CNS. <-- something we can/have learned from rat studies.

alas, the scientific community is hand-tied by a "code of ethics".

 

[endlessness]

So we can´t learn anything from animal studies regarding psychoactivity or toxicity? There are no useful indications?

 

[benzyme]

sure we can, qualitatively...I just don't buy quantitative determinations in rats as a direct correlation to human pharmacology.
bioavailability, enzymatic turnover, and half-life/excretion in humans is different from rats.

 

[The Neural]

I have to say, "what clues can we get from animal behaviours", is a discipline on its own. The literature is vast. But basically, it all begins by the establishment of clear observations.

A good example is the learned-helplessness paradigm, where the electrically shocked dog in a cage, after a specific amount of shocks, curls up and accepts the shocking, even if a hatch is opened after that amount of shocks are completed. After this paradigm, we can infer interactions with substances that e.g. cause the dog to actually leave the cage, where we will establish an intrinsic mechanism that is able to overcome the "learned-helplessness" state.

Water mazes and the behaviour of mice, when they give up trying and let go while in the water, is only logical to be linked to a form of "giving up" or more commonly used "depression", or more aptly put, "lack of motivation" (=reduced dopamine). So if you can induce reduced dopamine expression, you can normalize the observations and create measurements. E.g. These mice took 10mg of this substance, and gave up after 5 minutes, while the other mice took 50mg and gave up instantly, and make your inferences on this substance's effects on mice and their subsequent behaviour.

Needless to say, it all boils down to our own subjective (but collective) interpretations and attributions of gross generalisations. Most of the times, they are good for the purpose of a study, but as you pointed out, "twitching" could be anything, starting from the simplest motor neuron firing randomly, to a temporary action impairment caused by reduced dopamine binding or whatever.

That's why most animal models of psychiatric disorders are so severely scrutinised. A psychiatric disorder is so complex, that attributing and linking it to animals is a shot in the dark.

 

[The Neural]

So we can´t learn anything from animal studies regarding psychoactivity or toxicity? There are no useful indications?

sure we can, qualitatively...I just don't buy quantitative determinations in rats as a direct correlation to human pharmacology.

I agree with benzyme on this one. Anything further than observing that the mouse that received salvinorin A is now completely still (does not behave as the others who got sugar or saline or water) so its state is somehow "altered", is just speculation.

We could possibly infer the mechanisms with which e.g. scopolamine affects the hippocampus and prevents the formation of memories, and attempt to compare states of single neurons between species. Then we can say that this substance renders the action of those neurons similar, but that's as far as we can go. We can never find out if e.g. the "level" of psychoactivity is similar. We would have to ask the mouse...

 

[jamie]

I learned that humans can be really cruel, and make up reasons that they believe for why that cruelty is justified.

 

[a1pha]

I learned that humans can be really cruel, and make up reasons that they believe for why that cruelty is justified.

Not to get into a ´should animal studies be done´ argument, I´m just wondering about the studies that have been already performed, what kind of clues can we get from them?