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Re: Never thought I'd hear this..... » linkadge

Posted by SLS on March 18, 2006, at 7:29:51

In reply to Re: Never thought I'd hear this....., posted by linkadge on March 17, 2006, at 16:16:11

> >The only thing these models demonstrate is that >psychostimulants can produce in animals the same >behaviors that they produce in man. My belief
> >(currently) is that what psychostimulants >produce in a healthy (not bipolar) man is not >mania. Neither do antidepressants produce these >behaviors in animals. They only produce them in >man in association with affective disorder.

> It totally depends on your definition of mania. If mania is defined simply by symptoms and behaviors then yes, stimulants can cause mania.

There's the catch. Manji found that stimulants alone were not a valid model for mania because mood stabilizers would not attenuate the behaviors.

> If you define mania as being the result of a specific geneticly induced biochemical state, then no perhaps stimulants do not produce mania.

After reading Manji's work, I think that there are valid animal models for mania, but they have not been fully elucidated or evaluated yet. His adding of a BZD to AMPH probably works because the BZD produces disinhibition.

> But because your reaction took place while you were taking drugs, there is no conclusive way to tell if it was your genes or not.

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.

> As soon as you introduce that new variable, your personal biochemisty has been altered, and you can never be 100 percent certain that this is the way you would have reacted drug free.

It is how the alteration is expressed that demonstrates state-specific or trait-specific reactions that are reflective of that state or trait.

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.

> That may be the safest course to take, but I think there are a lot of peope who will fall through the cracks. Antidepressant treatments vary widely on their abilities to enhance dopaminergic function.

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.

> TCA's show the strongest ability to increase the sensitivity of limbic dopamine receptors.

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.

> They increase the sensitivity of d3 receptors in the neucleus accumbens, even in normal controll rats.

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.

> Anticholinergics can also cause mania, and psychotic reactions in healthy people.

Unless they are really occult bipolar. :-)

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.

> >It took at least 6 months to emerge. This is in contrast to stimulant-induced hyperlocomotive or psychotic states.

> TCA's effects on limbic dopamine receptors is acutally time dependant.
> D2, and D3 expression often increases significantly after many months of treatment. This happened in normal mice. The receptors increased their expression well above baseline, these were not stressed or depressed rats. They were rats that were about to have robuslty enhanced dopaminergic response.

This would be a good argument to support your contention that antidepressants can produce mania in non-bipolar individuals.

I don't see anything convincing enough to conclude one way or another based on the biological experiments and attendant inferences we have thusfar explored. I find your points compelling but not convincing. 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. 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'm still processing all of this stuff. Thanks for sharing your knowledge and understanding.


- Scott

 

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