Dr.Heckyll said:
It's also reasonable to think that the weight gain associated with many antidepressants and anitpsychotics is due to their 5-HT2C antagonistic activity.
Actually you can go one step further with this, because 5HT2C knockout mice show no developmental abnormalities, but become obese and are prone to epiletic siezures.
The obesity seems to be simply due to increase food intake, as animals given limited food don't become obese, but will if given free access to food.
Similarly microdialysis studies (in either wild type mice or rats, I can't remember which offhand) have shown that feeding increases dopamine release. 'Desirable' food (shortbread for example) causes greater DA release than normal food.
I think this has something to do with blood glucose levels, although I'm not sure.
So.......less 5HT2C activity=more dopamine
more blood glucose =more dopamine
The two together = lots more dopamine = positively reinforced behaviour and a very fat mouse!
As for the epilepsy, I'm not too sure, as 5HT2C antagonist don't cause seizures
seen in the knock outs.
I have heard 'scare stories' of stimulant induced seizures in people with no previous history of epilepsy. So either knockouts have even higher DA levels than those caused by antagonists.
Alternatively, 5HT2C is very heavily expressed in the hippocampus. I'm unsure if 5HT2C inhibits or stimulates the hippocampal activity, but my hunch is that 5HT2C is inhibitory.
How can DA cause an increase in feeding when stimulants generally inhibit it?
Any drug has what is described as a 'theraputic window' if the dosage is too low, it has no effect. If it's too high, it has unwanted side effects.
Dopamine works in the same way. Too low and you have a lack of response to positive stimuli. Too high and the same thing happens.
Fluctuations in and out of this window either above or below cause addictive behaviour. As will any sudden increases or decreases.
In the case of feeding, the connection between eating and dopamine release becomes learnt, but stimulants will 'uncouple' this as you get the dopamine release without eating (essentially it's tricked you brain into thinking you've eaten).
I don't think feeding's as simple as this, as there are alot of other important factors in feeding such as (CART, agouti, neuropeptide Y etc, etc), I can't substantiate it beyond anecdotally so I kinda have it as a 'work in progress'.