But I'm not familiar with this novelty-suppressed feeding test, is it an antidepressant test like the forced swimming test and olfactory bulbectomy?
Animals are hesitant to eat food in new environments (even if the food is well known) due to the stress of being in that environment. The latency before their eating reflects the level of anxiety induced by a known stressor (the new environment). Correct me if I'm wrong. So it's not really a measure of depression.
If this is an indicator for depression, then it surely would be a much more humane test than the forced swimming test.
So even if it is (I'm not sure) a good indicator for depression and the cascade you are outlining there is correct (which seems about right), then I still don't see how that could be the central mechanism for ketamine's antidepressant effects. It probably plays a role, but just look at how purely the approved 5HT1A agonist vilazodone is doing. It really doesn't seem to do any better than ssri's.
I'm just saying, it all seems like 5HT1A plays an important role, but it surely can't be the central mechanism, can it? There must be more profound mechanisms at work here other than increasing 5HT1Ar activity. I mentioned the fear-extinction for precisely that reason. It is very remarkable that a substance can extinct fears that have been acquired days earlier. 5HT1Ar activity seems like a dead end street to me, but I might be wrong.
Upon reading the article, the novelty-supressed feeding test IS in fact, I quote from the posted article: "useful for evaluating mechanisms responsible for actions of antidepressants."
It seems that the novelty induced supressed feeding test is usually only responsive to chronic antidepressant treatment, but not to acute or subchronic treatment. (Psychopharmacology (Berl). 2007 Mar;190(4):531-40. Epub 2006 Dec 13.)
However, it has apparently been shown that ketamine and some other related substances are an exception (Iijima M, Fukumoto K, Chaki S (2012) Acute and sustained effects of a metabotropic glutamate 5 receptor antagonist in the novelty-suppressed feeding test. Behav Brain Res 235:287–292; Koike H, Fukumoto K, Iijima M, Chaki S (2013) Role of BDNF/TrkB signaling in antidepressant-like effects of a group II metabotropic glutamate receptor antagonist in animal models of depression. Behav Brain Res 238:48–52)
I still don't know why they would pick this test instead of testing for behavioural despair (with supressed swimming) which seems of more interest when testing for antidepressant properties or am I wrong there?
My old criticism remains btw, can other depressants show any efficacy when an AMPAr or a 5HT1Ar antagonist has been given or when serotonine has been depleted (ofc not one that is directly countering the action of the respective drug)? Some 5HT1A activity seems obligatory in order for a rat/human not to be depressed.
I think it would have been interesting to observe the rats 3 days after the drugs had been administered or the serotonin depleted.
If the rats' depression had been attenuated by then, it would've demonstrated that said mechanism cannot block ketamine's antidepressant effects completely. Granted, it's unlikely, but it could've been interesting. Unfortuntely they killed the rats 18h later to verify depleted serotonin.
The only real question that remains is why they would chose that test over checking for behavioural despair with the forced swimming test. The fact that they don't name a reason for this strikes me as odd. There have been 2 studies that have shown that the antidepressants used show an immediate response in the novelty-induced hypophagia test, but that does not seem to be sufficient reason to use it, especially since ketamine has a significantly prolonged antidepressant action compared to other antidepressants and there seems to be no need to test for anxiety over behavioural despair.
Maybe this test is more common than I think, but I'm pretty sure that I usually see the forced-swimming used in similar scenarios and it seems more appropriate when testing for antidepressant action.
EDIT: Ok, forced-swimming supposedly has poor validity (construct and face), but I'm still not sure if that's the reason for using the suppressed feeding test, since it as I stated before tests for anxiety which is not very representative for depression unlike behavioural despair.