Posted by conundrum on February 22, 2010, at 10:00:20
In reply to D2 And 5HT2A: Dopamine Blocking And Boosting, posted by Brainbeard on July 17, 2009, at 5:32:24
>Stahl also says somewhere that D2-antagonism may be necessary for the pro-dopaminergic effects of .5HT2A-antagonism.
>What remains to be sorted out for me is what D2-antagonism actually entails and which parts of the brain are involved.
The following abstract may answer some of these questions. It seems that antagonizing the 5 HT2A may not lead to the dopaminergic pot of gold since it can reduce DA release in the Nucleus accumbens, but increases it in the medial prefrontal cortex. It also does nothing on its own to potentiate dopamine release. This could explain why trazodone isn't a very powerful antidepressant despite its strong 5 HT2A blockade. Nefazodone isn't much better and needs to be taken at a much higher concentration aroudn 300-600mgs to begin to engage the serotonin transporters.
"5-HT2A receptor antagonism potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and inhibits that in the nucleus accumbens in a dose-dependent manner
Abstract
Combined serotonin (5-HT)2A and dopamine (DA) D2 blockade has been shown to contribute to the ability of atypical antipsychotic drugs (APDs) to increase DA release in rat medial prefrontal cortex (mPFC). We provide additional support for this hypothesis by examining the effect of the selective 5-HT2A antagonist M100907 plus haloperidol, a potent D2 antagonist APD, on DA release in the mPFC and nucleus accumbens (NAC). Haloperidol (0.01–1.0 mg/kg) produced an inverted U-shaped increase in DA release in the mPFC, with a significant increase only at 0.1 mg/kg. Haloperidol (0.1 and 1.0 mg/kg) significantly increased DA release in the NAC.
****M100907 [5 HT2A antagonist](0.1 mg/kg) by itself had no effect on DA release in either region. ******This dose of M100907 potentiated the ability of low (0.01–0.1 mg/kg), but not high dose (0.3–1.0 mg/kg) haloperidol to increase mPFC DA release, whereas it abolished the effect of both 0.1 and 1.0 mg/kg haloperidol on NAC DA release. These results suggest that the relatively higher ratio of 5-HT2A to D2 antagonism may contribute to the potentiation of haloperidol-induced mPFC DA release, whereas 5-HT2A antagonism can diminish haloperidol-induced NAC DA release, even when combined with extensive D2 antagonism, which may not be synergistic with 5-HT2A antagonism in the mPFC."
Also I found another study showing that 5-HT2A antagonism blocks the release of dopamine in response to amphetamine in the Nucleus Accumbens and the striatum. However a 5-HT2B/C antagonist potentiates its release in response to morphine.
I'm just gonna post the link to that one:
http://www.nature.com/npp/journal/v26/n3/abs/1395776a.html
I wonder what the effects of these receptors is on NA release?
poster:conundrum
thread:907193
URL: http://www.dr-bob.org/babble/neuro/20091104/msgs/937672.html