Posted by linkadge on July 24, 2006, at 21:28:30
In reply to Re: what is my problem, posted by SLS on July 23, 2006, at 20:15:30
Its difficult to say. It is necesarry to to consider too whether the study is talking about 5-ht1a post synaptic receptors or presynaptic autoreceptors.
Sometimes serotonergic receptor alterations are used as justification for SSRI or MAOI treatment, without considering that the problem may lie elsewhere.
For instance, I was under the impression that post synaptic 5-ht1a recptors were upregulated in the frontal cortex suicide brain, as well as in schizophrenic patients. This may or may not have anything to do with the regulation of serotonin uptake. Serotonin 5-ht1a agonists like buspar, and clozapine have the ability to downregulate postsynaptic 5-ht1a receptors.
I think that upregulated 5-ht1a could be a result of some deficinacy of an endogenius serotonergic modulators like anandamide.
Anandamide potentiats 5-ht1a receptors and antagonizes 5-ht2a receptor responses (kind of like clozapine). Deficinacies in such agents could reusult in the abberent receptor binding found in some of these illnesses.
The below study says that presynaptic 5-ht1a autoreceptors are enriched in suicide victomes. I think this is referring to an enrichment of presynaptic autorecptors, which would resut in more inhibition of serotonin firing.
In this case, SSRI's work to downregulate autoreceptors. (At lest thats how I see it), resulting in more serotonin release. But, I have also seen that agents like buspar are able to achieve the same thing. So who knows how the autoreceptor became so overactive.
http://www.futurepundit.com/archives/001768.html
The below study suggests that 5-ht1a autoreceptors are upregulated in depression, which result in less serotonin release. Using buspar as a probe.
http://bjp.rcpsych.org/cgi/content/abstract/164/3/372
This study says the same thing.
I think that potent and selective 5-ht1a and 5-ht1b autoreceptor antagonists would result in immediate reduction in depression, since then you would not have to wait for any autorecptor downregulation to occur.
Lithium can have immediate antidepressant effects (through 5-ht1b autoreceptor antagonism). I'd like to see the effects of a lithium + pindolol combination. Lithium affects other things too. So, I think that immediate antidepressant effect can wane due to all the other stuff it does.
Pindolol kindof sucks because its not too strong an autoreceptor agtagonist, and it has post syntaptic antagonist properties too.
The body actually has an "endogenious" 5-ht1b autorecptor antagonist call the 5-ht moduline.
This is another potential target for psychiatry.
5-ht moduline works at nanomolecular concentrations to increase 5-ht release in certain areas of the brain.http://www.medscape.com/medline/abstract/12728412
ECT too, works to downregulate serotonin autoreceptors without effecting serotonin uptake at all. RTMs does the same thing.
I personally think that SERT has little to do with the origins of depression at all. I think its serotonin release that is the problem not serotonin uptake. SS may have more episodes of depression for different reasons altogether. Perhaps the extra serotonin in the amygdala makes them more sensitive to stress and depression.
Linkadge
poster:linkadge
thread:669157
URL: http://www.dr-bob.org/babble/20060724/msgs/670173.html