Hey Cumol , For my university (the college of wooster) we were required to start an original research project, design it with help from a faculty advisor, then carry it out, and write it up.

I had an interest in ketamine after reading a few articles suggesting that it had some antidepressant effects in small human studies. It is especially interesting for at least 3 reasons to my mind:

1. It has a very rapid onset, unlike traditional anti-depressants

2. In humans, it seems to have some serious longevity (1 dose, in a few studies, has led to people feeling significantly different for as long as a few weeks, some for over a month)

3. It seems (in humans) to be effective in patients who are resistant to traditional antidepressants.

Now, there is one big negative that leaps out at me; it is a drug of abuse, so there is potential in an at risk population (ie. those who are depressed) for some serious complications, if they were asked to self administer.

Now, we have quite a few small studies in humans, documenting that ketamine seems effective, and seems rather persistent after just a small dose. But in the papers I read through, it seems that you would be hard pressed to find anything so consistent in rodent models. Most studies in rodents dealt with serial doses, and those that dealt with acute doses had some very mixed results. I could dig out the paper if you are interested in this background.

My study was trying to see if previous studies had failed because of using different models of depression in the rodents, or if using different models would produce similar effects as we observe in human models. This is important because, as you probably know, animal models allow many times more subjects, and ones we care less about, than does human testing. If we could find a model which nicely correlates depression and ketamine treatment in rodents with the results already seen in humans, we could do quite a bit more preliminary testing, and boulster the idea of using it in humans.

Admittedly, this is not the most exciting project. Or, at least, not to the people I've talked to about it.

Anyway. The study went something like this: I used Wishart Rats (around 35 of them) I had 3 "Model of Depression" groups: Control, Chronic Moderate Stress, and Learned Helplessness. I had two Drug Conditions: Saline (control), and Ketamine. I evaluated the depressive symptoms via the Forced Swim Test. Basically, you're putting the subject in a tub of water they cannot escape from, and you compare active behaviors like swimming and climbing vs. inactive behaviors (floating), then use the relative amount of each behavior to judge "depression behaviors". I am not sure who came up with this, but it is fairly well regarded now, since SSRI's/other established anti-depressants tend to increase active and decrease passive behaviors when administered.

And I examined the effectiveness of the models at inducing depressive symptoms, and ketamine at treating the depressive symptoms.

Basically, there were no results to speak of. When we compared rats in the behavioral control condition to the other two groups (LH and CMS), we did not observe a significant difference. Which was disappointing to me, but that's how research goes sometimes, I suppose.

Anyway, I would have been curious to see some molecular measures of my study or a similar study (measuring BDNF perhaps?). I am curious to hear if you have any feedback on the study.

Molecular medicine sounds like a tough-as-nails proposition. Is that the field you currently work in?