Posted by linkadge on March 18, 2006, at 9:40:22
In reply to Re: Never thought I'd hear this..... » linkadge, posted by SLS on March 18, 2006, at 7:29:51
>There's the catch. Manji found that stimulants >alone were not a valid model for mania because >mood stabilizers would not attenuate the >behaviors.
I would disagree with that statment.
The following was taken from:
MANJI: Everything I said about antidepressants would apply to stimulants and maybe even more so. Enough stimulants seem to be capable of triggering manic-like episodes in anyone. In the lab, most of our animal models of mania are based on using stimulants. That is to say, we use repeated amphetamine administration to make the animal become sensitized so it shows high degrees of motor activity and hedonic [pleasure-seeking] behavior.
Interestingly, you can prevent this manic response to stimulants by pre-treating the animal with lithium. This is how we model human mania for our animal experiments. So if we have a new biochemical pathway that may work, one of the models we use is to treat animals with stimulants to make them hyperactive and then use this drug.
>I disagree. As in animal models, the specificity >of a reaction to a given drug can be determined >by producing strains sensitive to the assay.
Sure you can produce animals more sensitive to the stimulant properties of a drug. But again, this does not conclude that the animal would have ever become manic without the drugs.
>It is how the alteration is expressed that >demonstrates state-specific or trait-specific >reactions that are reflective of that state or >trait.
We are just not smart enough yet to develop a concrete model of exactly how genes and drugs interact.
>You once wrote that MAOIs were most likely to >produce a manic reaction. If my case is >representative of the majority, I would have to >agree with you.
They are broad spectrum drugs, and they often cause profound changes in sleeping patterns.
>At this point, I think it is important to >remember that the changes seen downstream of the >primary site of action of a drug is only an >association. In other words, the changes seen at >secondary sites might be a facilitative or >compensatory consequence for the activity >produced by manipulating the primary site.
Ok so its an association, just like the association that some forms of severe psychosis are associated with similar biochemical alterations.
>Sometimes, neuronal excitability increases >rather than downregulating with increased >activity. It is a positive feedback loop. Use it >or lose it. The D3 receptors might show >increased tone to reflect the increase in NE >signaling from sites upstream.
Not saying I know why it happens.
>I'll have to take your word for it. Psychotic >reactions I can see. I still have to question >what criteria were used to determine the >reactions to be manic rather than non-manic >psychotic.
Well they tend to make people giddy, euphoric, delerious, and can cause hallucinations.
>I find your points compelling but not >convincing.
I'm sure you've naturally considered such possibilites before. :)
>There is just so much to consider when it comes >to the brain and behavior. I think if it were >that easy to induce a true manic reaction in a >non-bipolar subject with antidepressants, we >would see much more of it.
We see an awefull lot of it. Enough of it that doctors are doing some of these stange things like revising the DSM, formulation new theories about the unification of bipolar and unipolar. Increase in SSRI/mood stabilizer combinations. New categories of bipolar. Statistically increased rates of suicide and agression in children treated with AD's. Bipolar has been called the "diagnosis du jour", this is a consequence of SSRI's inducing questionable behaviors. There is plenty of evidence available. Its just what picture you "want" to see.
>It is crucial to be able to differentiate mania >from other forms of psychoses and >hyperlocomotive states. If we see it happen to >5% of people diagnosed as being unipolar, that >about matches the rate of bipolar disorder seen >in the general population. However, I really >don't know what that rate is. I doubt it has >ever been studied, but it does seem to be rather >low based upon the frequency with which it is >reported.
I would disagree. I don't think that there would be multi-million doller research into the question as to whether SSRI's induce rapid cycling, if the statistics "fit nicely" into the presumed rate of bipolar.
>I'm still processing all of this stuff. Thanks >for sharing your knowledge and understanding.