With those requests in mind, here is a thorough explanation of what Dr. Zivago's lab is working toward. I'll level with you right now: the explanations--especially about depression--do get complicated. I've tried my damndest to make them clear, though.

So without further ado...

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In essence, we have two series of experiments going on in the lab right now:

1) Grettle's experiment series centers on Post-Traumatic Stress Disorder (PTSD). One of PTSD's characteristics is to show major testing deficits over all kinds of tests, from running a maze to color discrimination. PTSD rats, like humans, are slower to process because of brain trauma.

In an earlier study, though, Grettle showed that if you expose a rat to sucrose after they've encountered a traumatic episode (i.e. being shocked over an extended period of time), you can blunt or erase the deficits that the rat exhibits in a bunch of different tests. In other words, if the rats have experienced sucrose before the trauma, they go to town on the stuff and suck the bottle dry after being traumatized. Later one when they're tested with non-traumatized rats, these sucrose-sucking rats do about as well on various types of tests as the non-traumatized guys.

In the current experiment for her Master's degree in psychology, Grettle is looking at exactly when the rats suck down all this sucrose. Is it immediately after the trauma? A couple hours after? Right before they're about to be taken out of the cage (which in their minds means testing again)? We don't know.

Understanding just when the sucrose is consumed would let us know when the influx of sugar probably affects brain processing. Knowing exactly when this sucrose-sucking happens, we can examine brain tissue at that exact time and see what sucrose does in the brain to reverse PTSD's effects. Ideally, we could better understand the healing mechanism of sucrose and bring that knowledge to soldiers with PTSD or others.

2) The major project of the lab revolves around depression and how to reverse it on a chemical level. To cause depression in rats we use a drug called Reserpine. Reserpine was used as an anti-hypertension drug back in the 1950's. The major drawback to the drug, however, was that it made alot of its users depressed--to the point of needing hospitalization.

It was found that Reserpine depletes brain messenger chemicals called 'monoamines' by causing their transport containers to leak. Without those transporters, the monoamines can't move anywhere and are degraded. There are alot of famous brain chemicals that are monoamines, like Dopamine, Serotonin, Epinephrine/Adrenaline and Norepinephrine/Noradrenaline. An imbalance in any of these brain messengers will fuck you up good for at least 72 hours.

After 72 hours, the transport containers I mentioned refashion themselves and can ship the monoamines again. The restoration of the transporters allows your system to go back to its normal level of activity.

Interestingly, Depression seems to act by at least two different mechanisms. As I mentioned, Reserpine has a time course of at least 72 hours. Reserpine acts differently at two different time periods, at an early component time and a late component time.

The early component time period is from 1-24 hours. This early component of depression occurs without any influence from the immune system. The late component time period is from 48-72 hours. This late component depression, in contrast to the early component, actually IS influenced by activity in the immune system.

This first part of the research is very important because it shows that Depression isn't just a mental disorder, it's actually a disease--just like the flu or AIDS. We believe this because this late component of depression can be influenced by the immune system. One of the criteria for a disease being a disease is that it causes or can be influenced by an immune response.

So, the next logical question is this: what kind of a disease is Depression? the answer is that it's probably a metabolic disease. For our purposes, metabolism refers to the total amount of blood sugar ("energy") in your system that you've got stored and the amount of energy that you're using at a given time. Normally, the amount of energy you burn and the amount of energy you store don't get grossly out of whack.

In 'normal' people, the only way this energy balance does gets grossly out of whack is if your system is majorly stressed for a long period of time. This long-term stress could be caused by an extended chase from a giant spider or cheetah, a series of emotionally devastating events or anything that you yourself perceive as being stressful that happens for a long time.

For Depression to occur, we think, the body needs to enter a state where several things have occurred:

*The amount of blood sugar (or energy) that the body needs to adequately functions exceeds the amount of energy it has in circulation.

*There is a majorly stressful or taxing event that is simultaneously happening to you.

*You believe you lack control over this majorly stressful situation--or that you cannot predict what the fuck is going to happen to you (e.g. being tortured by the secret police).

The lack of adequate energy levels and the stress on your system causes your brain to go into metabolic withdrawl. This metabolic withdrawl has to occur. If it didn't happen, the cells in your brain would keep furiously trying to process stressful shit and would go into toxic shock. Your brain would quickly overload, get massively damaged and you would soon die.

To cause this metabolic withdrawl, your brain releases a chemical called Adeonsine. Adenosine is the most powerful brain cell and brain tissue inhibitor in the brain--period. For example, Adenosine is released for three seconds but causes brain lockdown to occur for many days afterwards.

With all that background in mind, Depression seems to be a condition where this metabolic withdrawl or lockdown happens for a very long period of time.

Somehow, either adenosine (the POTENT inhibitor) itself or the activation patterns it originally created are continously accessed on a regular basis. So even though whatever was originally stressing you has vanished, your body and brain go into this same withdrawl state when even a tiny negative event happens to you.

Basically, your body and brain 'think' this tiny event is as bad as the original one that was majorly stressful. As a result, you shut down emotionally, mentally and physically--all because your body desperately wants to hold onto as much energy as it can.

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I know I've probably confused you by now, but bear with me and just remember that adenosine is the pimp daddy of depression--it gives you the smack down and commands when your arse gets depressed.

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Now, remember when I mentioned the early component and late components of Depression? How the early component isn't affected by the immune system, but somehow the late component is affected by it? Well, when you inject an adenosine blocker into the brain, you instantly--and I mean instantly--reverse Depression in an animal that was injected with the depression-causing drug Reserpine (which as you might recall depletes brain chemicals).

Adenosine thus seems to be the light switch of depression.

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What we're trying to figure out right now is how the pimp daddy--Adenosine--smacks the ever loving hell out of your arse and makes you depressed. Moreso, we want to figure out just why an adenosine blocker instantly reverses the effects of depression. Some more questions are: how does the immune system affect the pimp daddy? How does pimp daddy affect the immune system?

If we can figure out how adenosine lords itself over your body, we could potentially find a way to instantly reverse depression--all forms of depression, without any of the side effects of SSRI's, tricyclics or electro-convulsive shock therapy.

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So as you see, the shit we're working on with depression is fascinating. Basically I'm trying to replicate the results I just mentioned to you.

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That was probably way too much information, but that is the full picture of what we do in the lab. If you have any questions, by all means ask.

Also, don't think I'm wicked smart for outlining all of that info or that you're dumb for not understanding it all. It took me 2 months to fully appreciate all the shit we are doing.

That said, happy 4th of July for my fellow Yankees--and happy ordinary day for everyone else.

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