Comment · Tue, January 28, 2014
Effects of sustained serotonin reuptake inhibition on the firing of dopamine neurons in the rat ventral tegmental area
What they were answering
[deleted] · 9 points
Some excerpts from the abstract sum this up very well (emphasis mine).
Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are efficacious in depression because of their ability to increase 5-HT neurotransmission. However, owing to a purported inhibitory effect of 5-HT on dopamine (DA) neuronal activity in the ventral tegmental area (VTA), this increase in 5-HT transmission might result in a suppression of the firing activity of DA neurons. Since the mesolimbic DA system plays an important role in motivation and reward, a potential decrease in the firing of DA neurons may lead, in some patients, to a lack of adequate response to SSRIs.
The difference between escitalopram and citalopram in their effect on DA neuronal activity may be explained by the higher efficacy of escitalopram as a 5-HT reuptake inhibitor. Since the inhibitory effect of escitalopram on DA neuronal activity is mediated via 5-HT2C receptors, antagonists of these receptors might be effective adjuncts in SSRI-resistant depression.
I don't know what to think of the 5-HT2C receptor, overall. 5-HT2C knockout mice are obese and more susceptible to seizures than those that have it, which makes me think blocking it might not be best idea in the world.
5-HT2C agonists have been researched for treating nicotine addiction and as anorectics (appetite suppressants).
These days I'm taking a combination…
u/MisterYouAreSoDumb
Then you have the other side to the story, 5-HT2B and 5-HT1B.
http://www.ncbi.nlm.nih.gov/pubmed/16885935
Pretreatment with MDMA or stress alone blunted MDMA-induced 5-HT release in the VTA. The augmentation of MDMA-induced DA release in rats pretreated with MDMA+chronic stress was attenuated by perfusion of the 5-HT(1B) antagonist, GR127935 into the VTA before the MDMA challenge injection. These results suggest that prior exposure to both MDMA and stress can produce a long-term augmentation in mesolimbic DA transmission and enhanced drug abuse vulnerability that is mediated, in part, by the 5-HT(1B) receptor in the VTA.
So it looks like 5-HT1B receptors in the ventral tegmental area also mediate the release of dopamine.
Then you have:
http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2004.02763.x/pdf
These results suggest that MDMA-mediated increases in DA within the NAC shell are dampened by increases in VTA GABA subsequent to activation of 5-HT 2B/2C receptors in the VTA.
So it looks like 5-HT2B/C activation in the VTA also stimulates release of GABA, and increases dopamine release in the nucleus accumbens.
Sorry to derail the SSRI focus, but your post got me thinking about the mesolimbic dopamine pathway, and how serotonin receptor activation modulates it.