Posted by SLS on November 15, 2010, at 6:05:10
In reply to Re: Vilazodone vs Nefazodone - 5-HT receptors, posted by linkadge on November 14, 2010, at 20:12:24
> Necessarily not true. When given acutely maybe, but there are conflicting reports as to whether chronic administration of SSRIs actually increases serotonin neurotransmission. There are many compensatory changes that occur when SSRRIs are administered chronicaly.
Yes. I was thinking that maybe a downregulation of presynaptic serotonin receptors in response to the dramatic and chronic increases in synaptic neurotransmitter would explain the increase in synthesis and, perhaps, release of serotonin. With the concentration of synaptic serotonin being kept artificially high, postsynaptic receptors will continue to be stimulated. The effect might be to increase synaptic serotonin acutely, but decrease the signal-to-noise ratio as the postsynaptic neuron remains partially depolarized. After chronic administration and the resulting reduction in postsynaptic receptor numbers, a new dynamic equilibrium is established, ultimately restoring or even enhancing the signal-to-noise ratio.
I am somewhat confused about all of this. There is so much more to be considered, as you demonstrated better than I could. I have always wondered if pushing the system in either direction causes a reset of the homeostatic "thermostat" to a new equilibrium that more closely resembles a normal dynamic. This notion might explain the effectiveness of both serotonin reuptake inhibitors (fluoxetine) and reuptake enhancers (tianeptine).
> According to wikipedia: "Certain SSRI medications have been shown to lower serotonin levels below the baseline after chronic use, despite initial increases in serotonin"
Okay. now I'm really confused.
http://molpharm.aspetjournals.org/content/61/4/778.short
"Up-Regulation of Tryptophan Hydroxylase Expression and Serotonin Synthesis by Sertraline"
Oh, well.
- Scott
Some see things as they are and ask why.
I dream of things that never were and ask why not.
poster:SLS
thread:970074
URL: http://www.dr-bob.org/babble/20101107/msgs/970310.html