Copy of a post of me on another forum:
5HT2A also plays a role in prozac's dopamine increase:
In another study, injections of M100907 attenuated fluoxetine-induced
increases in cortical DA (Zhang et al., 2000). Thus, selective antagonism of 5-HT2A receptors
attenuates mesocortical DA release.
Comes from this paper:
Besides, some interesting facts about 5HT2A:
Atypical, but not typical, antipsychotic drugs robustly increase DA release in the PFC. A
common property of these drugs that distinguishes them from the typical agents is high affinity
for the 5-HT2A receptor. Thus, a plausible hypothesis was that 5-HT2A receptor antagonism
increases cortical DA efflux. Earlier studies demonstrated that administration of the nonselective
5-HT2 receptor antagonist ritanserin increased nigrostriatal and mesocorticolimbic
DA efflux (Devaud et al., 1992; Pehek, 1996; Pehek and Bi, 1997). However, subsequent work
has shown that ritanserin may facilitate DA cell activity by antagonizing D2 receptors (Shi et
al., 1995). Multiple subsequent studies have since been performed with the selective 5-HT2A
receptor antagonist M100907 and demonstrate that systemic or intracortical administration
Alex and Pehek Page 11
Pharmacol Ther. Author manuscript; available in PMC 2008 October 7.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
blocks DA release evoked by treatment with the 5-HT2 receptor agonist DOI (Gobert and
Millan, 1999; Pehek et al., 2001).
In contrast to studies employing the administration of 5-HT2A receptor antagonists alone, the
combined, systemic administration of D2 and 5-HT2A receptor antagonists results in a
potentiation of cortical DA release (Westerink et al., 2001; Liegeois et al., 2002). Evidence
has been provided that this effect may be mediated by actions of released 5-HT interacting
with 5-HT1A receptors (Bonaccorso et al., 2002). In addition, this potentiation may result from
actions of drugs on DA cells in the VTA. It is clear that, as a class, atypical antipsychotic drugs
enhance DA release in the PFC. It is also clear that this effect is not mimicked by selective
antagonism of 5-HT2A receptors. Rather, it may result from a combination of receptor binding
properties including blockade of 5-HT2C receptors (see below).
demonstrated that intracortical infusions of the 5-HT2A receptor antagonists M100907 or MDL
11,939 blocked the increases in cortical DA produced by the systemic administration of the 5-
HT2 receptor agonist DOI (Pehek et al., 2001; Pehek et al., 2006).
Recent behavioral studies demonstrate that selective 5-HT2A receptor blockade attenuates
DA-mediated behaviors. Administration of the 5-HT2A antagonist SR 46349B (1.0 mg/kg or
less) attenuates hyperactivity induced by either the acute or repeated administration of cocaine
(Filip et al., 2004). Treatment with M100907 reversed behavioral deficits in locomotor activity
and prepulse inhibition of acoustic startle in DAT knockout mice (Barr et al., 2004). In addition
to behavioral abnormalities, these mice display elevated synaptic levels of DA (Gainetdinov
et al., 1999). The authors suggest that 5-HT2A antagonists may be useful in the treatment of
conditions characterized by chronic, elevated dopaminergic tone.
Activation of 5-HT2A receptors stimulates dopaminergic activity in all three pathways
although most work has been performed in the mesocortical system. Investigations into the
circuitry of this regulation indicate that 5-HT2A receptors on corticotegmental projections
regulate DA cellular activity. A functional role for 5-HT2A receptors localized on VTA DA
neurons remains to be determined.
5HT2A antagonism on its own doesnt increase cortical dopamine at all, instead it appears that agonism actually increases dopamine in several brain area's. Ive never really jumped on the anti 5HT2A bandwagon, but many ppl still think that 5HT2A antagonism is a good thing, i have to disagree with that.
5HT2A facilates dopamine release and 5HT2A antagonism does NOT raise dopamine.