Posted by linkadge on December 21, 2008, at 22:34:13
In reply to Re: Agomelatin: could 5HT(2c) action be bad for sl » psychobot5000, posted by Marty on December 21, 2008, at 17:10:44
Yes, 5-ht2c agonists have antidepressant properties too. I personally think that there is a normal circadian regulation of 5-ht2c function which may become disturbed in depression. I know that HGH acts as a functional 5-ht2c antagonist.
5-ht2c agonists increase climbing behavior in the forced swim test in mice.
A 5-ht2c agonist might have more application in depression associated with hyperactive frontal cortex function (for instance OCD/Depression). A 5-ht2c agonist might also work well with atypical depression depression that is associated with overeating etc.
The other thing too is that a 5-ht2c agonist would likely downregulate these receptors so that DA output is enhanced as the drug starts to wear off. Thats why I really think it is more about regulation. You need the receptors to be active at certain times of the day and then less responsive at others.
The 5-ht2c receptors are involved in declarative memory. 5-ht2c receptor antagonists can block declaritive memory retrieval they can also block the memory for certain escape related behaviors in mice.
I see it like this, you need the 5-ht2c antagonist so that you have enough executive function to sustain certain tasks. After an activity is sustained for a period of time, the 5-ht2c receptors kick in so that you can 'pull out' of the behavior and 'reflect' on the processes that you have been performing. 5-ht2c agonism is only good for memory retrieval if you have learned the task, it can also increase the ability to think abstractly and laterally to help compare and relate ideas.
So if you're one of those people who doesn't want to initiate a task because you think you know it all, you might need some 5-ht2c antagonism. However if you are not getting enought 5-ht2c antagonism you might have trouble stopping behaviors and/or realizing what you have learned / the bigger picture.
Also, there is crosstalk between the 5-ht2c receptors and 5-ht1b receptors. Apparently 5-ht2c agonism decreases the responsiveness of postsynaptic 5-ht2b receptors which are involved in reward function and certain spatial memory functions. So althought 5-ht2c antagonism acutely decreases declaritive memory, it may increase performance in certain spacial learning tasks.
So, the antideprssant effects of 5-ht2c antagonism may infact be partially mediated by a corresponding increase in 5-ht1b receptor function.
The reason that a 5-ht2c agonist might help in schizohprenia is perhaps due to an anticonvulsant effect. Also, the 5-ht2c receptors are involved in some form of synaptic pruning if I recall.
poster:linkadge
thread:869924
URL: http://www.dr-bob.org/babble/20081214/msgs/870194.html