Animal models of Depression

In paper citation (Deussing, 2006).

I have been curious about what sorts of animal models of depression exist because I am already thinking about developing experiments related to depression and sleep.

First of all, I am thoroughly dissatisfied by the two most common methods for assessing despair in rodents: the forced swim test and the tail suspension test. This is because they are acutely sensitive to the administration of antidepressants, and we know that antidepressants typically take about four weeks to display therapeutic effects. Furthermore, when suspending a male rodent from his tail, he receives a huge surge of testosterone from his testes because this is the area manipulated by the tail-suspension test. Tail suspension is very abnormal, and so are testosterone surges.

Also, do humans show an immediate decrease in despair after taking antidepressants? I feel like I would have heard about it if this were the case, but I have not. I have heard that more people commit suicide in those first few weeks, but I have never heard this directly linked to acutely increased motivation (like the motivation to swim or struggle in the rodent tests). We should have a better human correlate than the motivation to kill oneself.

My three favorite tests of depression are the sucrose preference test, the novelty-induced hypophagia test, and the dexamethasone suppression test. The sucrose preference test measures a rodent's motivation to seek rewarding stimuli (such as sugar in the water) and is sensitive to chronic antidepressant treatment. The novelty-induced hypophagia measures a rodent's anxiety level by presenting the rodent with a conflict. The rodent is faced with a desirable food item inside of a novel environment. It can either avoid a novel environment, or enter the novel environment and consume the food. The biggest problem with this paradigm is that it measures anxiety, not depression, and some rodents never choose to consume the novel food. The dexamethasone suppression  test looks at the ability of a synthetic glucocorticoid to downregulate glucocorticoid expression.This basically measures the neuroendocrine health of the rodent.

In terms of creating depression in a rodent, my three favorite methods are via social stress, maternal deprivation in the first two weeks of life, and olfactory bulbectomy. Social stress is most like human stress, but is not as reproducible as learned helplessness paradigms. Similarly, early life stress is less reproducible, and has not been tested with the typical antidepressants yet (which I find shocking!). Finally, the olfactory bulbectomy is easiest to do in mothers shipped from the rat factory.  However, I am not so certain how to make rat mothers depressed and not just stressed. Is it even possible to isolate the two? Time will tell.