Posted by zeugma on December 28, 2005, at 21:10:18
In reply to Re: what is Fos-Immunoreactivity? » zeugma, posted by Larry Hoover on December 27, 2005, at 11:42:03
d c-Fos:
> >
> > http://www.pubmedcentral.gov/picrender.fcgi?artid=1188655&blobtype=pdf
> >
> > apparently iprindole and nortriptyline are more selective in their neuronal activation effects than any of the miscellany of other AD's tested. perhaps you can help interpret the results' significance (if any), since the authors don't seem to know what to make of it.
>
> Interpret? That's where I least like to step beyond the descriptive. In such a complex system, we do not know that an activated neuronal network represents even so much as an excitatory or an inhibitory complex. Let alone our fragmentary sense of how the pieces fit together. Or that the observed brains were not even primate. >>That the observed brains were not primate doesn't bother me, since I have to take it on faith that most of these studies are written by possessors of primate brains.
(Ok, I've gotten that bit of bile against drug researchers out of my system. I feel better now.)
The reason the c-fos study intrigued me was because many the drugs I've had the fortune to ingest did have effects that were immediate, more or less. And this often cut across 'class' lines, i.e., nortriptyline and modafinil had similar immediate effects in me, a marked slowing of thought processes that I *believe* constitutes an 'antidepressant' effect in me. While methylphenidate actually had a less marked immediate effect (of course dose could play a role here) but there was no slowing of thought processes involved. And the drug intensified depression, as did atomoxetine, a drug that improved focus markedly (like methyphenidate) but lacked this 'slowing' effect. Now much of the justification for atomoxetine's being an effective ADHD treatment, but not AD, hinged on its putative differential site of action (the prefrontal cortex is very fashionable now, and everything from Zyprexa to Wellbutrin 'preferentially increases dopamine in the prefrontal cortex.')
For the record, I believe atomoxetine is an AD, but not a good one because it has other effects that eventually negate its AD effect. But that is just my opinion.
>
> C-fos signalling is so fundamental a response to receptor complex formation that it is perhaps the least discriminative of any possible marker for activation. This link gives some sense of what I mean: http://cellbio.med.harvard.edu/faculty/blenis/pdf/N_and_V_for_Murphy_et_al_Assoian.pdf
>
> The work in question, above, is very old. And I don't know what it shows us, other than we can localize some of the immediate chemical effects of psychoactive drugs. Until we can discriminate between different types of activation, I don't know that we gain much knowledge from this study, other than inferential with respect to how the brain is organized. And that presupposes that we understand the difference between acute and chronic drug exposure.
>
yes, but i am interested in acute effects, even though they do not result in mood elevation as such. the hypothesis of the authors of the old study was that the immediate effects are causally related to the later, AD ones. i realize this is a debatable assumption, but it bears investigation.
> > this is an update from this year:
> >
> > http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15812568&query_hl=670&itool=pubmed_docsum
> >
> > -z
>
> I think the latter paper states much the same as I have suggested, that c-fos mapping is an investigative/screening type tool. By showing chemical activation of certain physical structures, a putative antidepressant molecule might be crudely assessed for activity, but we risk both types of hypothesis-testing error, yet. Stimulation of the selected brain complexes may not be unique to antidepressant activity, and antidepressant performance may be possible when such activation is absent.
>
Certainly. But the central nucleus of the amygdala is implicated in affective states. And if, for instance, atomoxetine did activate this structure, but was not an AD, this would bear investigation. granting that an assumption is made that such a structure is implicated, the question would be whether this structure was sufficient, or merely necessary, to elicit an AD effect. Perhaps atomoxetine's other effects, besides NE reuptake inhibition, somehow affect affective networks in a different way than desipramine, which it otherwise resembles pharmacologically- and perhaps also there is no common site of AD action , which would be a good thing to know, so as to rely more heavily on behavioral studies, or resign ourselves to the fact that AD's are about as good as they can get, since we have isolated mechanisms of AD action (monoaminergic neurotransmission) and perhaps others will turn up, but fortuitiously.> I'm very harsh in my analysis of this sort of research, because there is a significant risk of "begging the question", petitio principii. We may see patterns that don't exist, simply because we believe in the existence of the pattern itself.
>it is better to be harsh with such research than to beg the question. the main research, in truth, i have done is on myself. from this i DO think that immediate effects of psychotropics bear on the outcome of the treatment. hence i think the assumption of the authors of the study is a plausible one. and that c-fos however crude a marker is a place to start. but neither nortriptyline nor modafinil are beneficial in all depressions, and the fact that a drug activates a particular structure then is an interesting coincidence until the structure can be shown to play an integral role in mediating an AD response in *very* different brains (say, those who get an AD effect from bupropion, which i could not tolerate at all- strictly speaking then i should say that it was side effects that were too severe, not inefficacy.)
your reply was most gratifying to me. i should comment again on this topc when i've read "Synaptic Self" again (he has done a lot of work on the amygdala-certainly there are worse ways to pass the time).
-z
poster:zeugma
thread:590496
URL: http://www.dr-bob.org/babble/20051221/msgs/592902.html