Posted by linkadge on December 27, 2011, at 20:30:14
In reply to Re: lithium 5-ht1b + gsk-3b, posted by SLS on December 26, 2011, at 11:19:48
>Another involves the inhibition of dopamine >receptor glycogen synthase kinase-3 (GSK-3) >signalling. Note that these explain mania rather >than depression.
Gsk-3b inhibitors have *some* antidepressant effects. GSK-3b is increased by dopaminergics (d2 activation) (i.e. psychostimulants) and decreased by serotonergics. In mice lacking trytophoan hydroxylase, gsk-3b is upregulated. The behavioral dysregulation in these mice can be reversed with selective gsk-3b inhibitors.
Schizophrenic symptoms appear to be ameleorated in mice with selective gsk-3b inhibitors.
Also, gsk-3b inhibitors have substantial neurotrophic effects. Selective gsk-3b inhibitors mimic many of the trophic effects of lithium and valproate.
I think I remember reading one study that said fluoxetine was a gsk-3b inhibitor. Oh here it is...It also shows that imipramine, clorgyline and fenfluramine indirectly inhibit gsk-3b.
http://www.nature.com/npp/journal/v29/n8/full/1300439a.html
Anyhow, gks-3b is an interesting target for certain mood disorders because it interacts with circadian genes, as well as the regulation of the 5-ht1b receptor, which is critical in the control of limbic serotonin.
poster:linkadge
thread:1005569
URL: http://www.dr-bob.org/babble/20111226/msgs/1005681.html