Posted by undopaminergic on May 26, 2008, at 15:05:18
In reply to GREAT topic -- my answer is 'No, but...' » SLS, posted by Racer on May 26, 2008, at 10:13:25
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> In the course of my readings, I've found some interesting articles that make me much more skeptical about any putative one-to-one relationship between medications and neurochemicals.
>It's wise to keep an open mind about the potential for undiscovered properties of drugs. Most compounds have not even been tested for their possible binding affinity to most of the known receptors, enzymes and other targets, not to mention the targets that remain unknown to science.
> For instance, did you know that Ritalin reduces the ADHD-like symptoms in dopamine knock-out mice? These are mice without active dopamine receptors -- and yet, we discuss Ritalin as a dopaminergic medication. That seems to suggest -- strongly -- to me that boosting the action of dopamine is probably not the solution to ADHD-like symptoms, it's probably not how Ritalin actually works. Or, at least, it's not the whole story.
>You are probably thinking of dopamine transporter knockout (DAT-KO) mice, because mice lacking dopamine receptors would presumably suffer from extreme parkinsonism, and quite possibly worse. You may also be confusing cocaine with methylphenidate - although these drugs are similar in many ways, methylphenidate lacks the serotonin reuptake inhibition that seems to account for the major effects of cocaine in DAT-KO mice. The case of the DAT-KO mice also illustrates the dangers of making generalisations based on results from experiments with genetically modified organisms: the lack of the dopamine transporter influences the development of the mice physiologically and behaviourally - for example, their weight is lower, their wakefulness and activity level enhanced (and sleep reduced), and they are hypersensitive to the stimulant effects of caffeine but have reduced sensitivity to cocaine, amphetamine, and modafinil.
It's true that dopamine is not the whole story in the case of ADD/ADHD, but it does seem to play the major role; noradrenaline also seems to be high significance, whereas serotonin appears to be a factor of little importance - probably less than glutamate.
> What's more, I don't believe that there is one disorder called Depression. I believe that there are clusters of symptoms which we group together for convenience sake, and call Depression.
>That's a very accurate conclusion. Some concepts of different subtypes of depression - such as melancholic and atypical - have already long been used, especially in research, but these subtypes are based on clusters of symptoms that can be observed. I think more focus on the etiology of these conditions and the underlying neurobiological substrates would be more useful, not only from a theoretical standpoint but even more so from the practical point of view of psychopharmacological treatment.
poster:undopaminergic
thread:830457
URL: http://www.dr-bob.org/babble/20080519/msgs/831224.html