Nov 30 2010 Published by scicurious under Basic Science Posts
Sci's over at Scientific American today, giving a guest post on the recent findings of reboxetine...the antidepressant that couldn't.
3 responses so far
I am so proud to see a Scientopian at SciAm.
I know it's (extremely) early to say, but what are the most likely explanations for why it failed, do you think? Is there a shortlist of potential differences between the model animals and humans' neurochemical makeup that might have caused it, or is it more likely to be a more fundamental problem with the way depression is being modeled in animals?
It is very early to say, but my personal opinion is that it's a fundamental problem with the way we model depression in animals.
Basically, most diseases (including many psychiatric diseases) have very solid symptomatology. For example: ADHD. Lack of attention/focus, hyperactivity. People who do not have these symptoms do not have ADHD. It's that simple. But depression is a VERY difficult thing to quantify. You could have two people with depression who have NO overlapping symptoms. And so models only get at some of the symptoms which some people experience.
Our current models like forced swim and tail suspension get at mechanisms of coping, separating it into active (swimming or struggle) and passive (floating or hanging) types of coping, with the passive deemed 'pro-depressive'. This isn't wholly inaccurate to the human condition, but it's clear that while it can pick out a lot of drugs that work in humans, it lets false positives through. For example, changes in locomotor activity (though we usually control for that) but also the question of which type of coping is "better" or "more adaptive". Some may say (and they might not be wrong), that "passive" coping when you're in a situation that you can't get out of (like strung up by your tail) is in fact BETTER. But what does this have to do with antidepressant activity? Dang if I know.
I would say we may have more success using models, like sucrose drinking or pursuit of sexual or social contact. These models get at aspects of anhedonia, or the inability to experience pleasure, which is one of the more universal symptoms of depression, and which I think may be able to detect more useful aspects of antidepressant activity.
But that's just me. That's all opinion right there. 🙂
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