To really answer your question appropriately we need a bit more information. Are you looking to acutely stress the mice, and look at acute responses? Or looking for more chronic stressors that eventually lead to the development of depression like phenotypes? Since it looks like you are interested in neurogenesis, I am guessing chronic stressors are more appropriate.

I would agree with Casadei's answer the most, and look into using some variation of chronic mild (aka chronic unpredictable and chronic variable) stress protocols. If you are looking for an even more robust stressor that is known to regulate neurogenesis, chronic social defeat stress may also be worth looking into.

Social defeat stress is known to induce deficits in neurogenesis, as well as involve some hormonal responses (interestingly not testosterone though) in that process. See this recent McEwen article (http://www.ncbi.nlm.nih.gov/pubmed/20732337).

These two papers are worth looking into for some background on social defeat in mice:

http://www.ncbi.nlm.nih.gov/pubmed/16469931

http://www.ncbi.nlm.nih.gov/pubmed/17956738

And finally here is a protocols paper which makes some of the details more clear:

http://www.ncbi.nlm.nih.gov/pubmed/21799487

Hope this helps.

Mice are very sensitive to noise, so, I'm pretty sure you will get them stressed out if you are able to make a loud sound after a period of quietness. Mice have sensitive ears....Hope this helps!

There are several well documented stress protocols for mice. One of the most common is restraint stress where the mouse is placed in a 50ml conical tube that has a lot of holes (for air circulation). This prevents the mouse from moving around and is very stressful (30 min to 1hr is plenty). Another method is social housing. If you change the cagemates twice a week, this is also stressful as the mice must reaffirm their 'dominance'. Works well for both males and females.

Hope this helps.

in addition to above, isolation of pup from mother, sleep deprivation through mechanical disturbance or other means, can also be used. Another thing I would try is use of dim light. In humans it is well known that dim light increases the propensity of the individual to undergo depression and is one of the causes of seasonal affected disorders in humans... I have not read any such papers wrt mice but am sure it must be done....

Mice are also stressed when being housed alone. Furthermore I remember that another group from my university used heat stress. Mice were regularly exposed to moderately elevated temperatures (look on pubmed for exact protocols), hope that helps

First of all, take really care that the ethic comity of your country will accept your experimental plan, because these protocols are difficult to get validated!

Their are plenty of protocol for it, I would say that the most commun is the mild stress protoco as described here: PLoS One. 2009;4(1):e4326. Epub 2009 Jan 29. Chronic mild stress (CMS) in mice: of anhedonia, 'anomalous anxiolysis' and activity. Schweizer MC , Henniger MS , Sillaber I .

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004326

It was review intensively there

Psychopharmacology (Berl). 1997 Dec;134(4):319-29. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Willner P

http://www.springerlink.com/content/5da9w1qgul1b7gb2/

To really answer your question appropriately we need a bit more information. Are you looking to acutely stress the mice, and look at acute responses? Or looking for more chronic stressors that eventually lead to the development of depression like phenotypes? Since it looks like you are interested in neurogenesis, I am guessing chronic stressors are more appropriate.

I would agree with Casadei's answer the most, and look into using some variation of chronic mild (aka chronic unpredictable and chronic variable) stress protocols. If you are looking for an even more robust stressor that is known to regulate neurogenesis, chronic social defeat stress may also be worth looking into.

Social defeat stress is known to induce deficits in neurogenesis, as well as involve some hormonal responses (interestingly not testosterone though) in that process. See this recent McEwen article (http://www.ncbi.nlm.nih.gov/pubmed/20732337).

These two papers are worth looking into for some background on social defeat in mice:

http://www.ncbi.nlm.nih.gov/pubmed/16469931

http://www.ncbi.nlm.nih.gov/pubmed/17956738

And finally here is a protocols paper which makes some of the details more clear:

http://www.ncbi.nlm.nih.gov/pubmed/21799487

Hope this helps.

Nice post Sam!

Any adaptation of social defeat on females?

Unfortunately not, which is a major draw-back to using social defeat models. Female mice, for the most part, will not engage in antagonistic interactions, and if you use a male aggressor.... defeat is not what happens. That said, some intrepid labs have attempted to adapt the model for females with some success.

First, very recently there has been some work adapting the defeat model to California mice, which are actually a member of the Vole family.

http://www.ncbi.nlm.nih.gov/pubmed/21364768

Second, the is a lactating dam model for rats (and maybe mice as well?) which also works.

http://www.ncbi.nlm.nih.gov/pubmed/15896920

Both of these get out of the standard mice models, however, and the lactating dam model requires the herculean effort of breeding and timing the aggressors within small windows of pregnancy.

When we do gender work, we stick to chronic unpredictable stress protocols.

I agree, chronic unpredictable stress is the way to go. There are a lot of stress protocols out there that are either not hugely ecologically relevant, easily adapted to or not as stressful as one might think.

Whatever you choose, think about adaptation and learning if you are repeating the stressor and keep a close eye on 'collateral' stress (having to move the mice or change cages. Some of these unintended stressors may be more stressful than your treatment.

Look up Eric Nestler's work. They pair submissives with very aggressives. It seems to be quite effective.

1h of water avoidance stress (acute or chronic) is an extremely reliable, well-published example of psychological stress. It reliably activates the HPA-axis axis and causes increased intestinal permeability. It is not in any way painful so it is easy to get approval by animal care committees.

The CUS protocols work well. You can validate an effect on mood by doing a test for anhedonia like the sucrose preference test.