Posted by Larry Hoover on December 27, 2005, at 11:42:03
In reply to Re: what is Fos-Immunoreactivity? » Larry Hoover, posted by zeugma on December 24, 2005, at 18:43:15
> hi larry,
>
> hope you're having a good holiday.Thanks. Same back at ya.
> i dug up this trove on antidepressants and 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.
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.
> 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
>
> -zI 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.
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.
Best,
Lar
poster:Larry Hoover
thread:590496
URL: http://www.dr-bob.org/babble/20051221/msgs/592408.html