The activation of 5‐HT2A receptors in prefrontal cortex enhances dopaminergic activity

@article{Bortolozzi2005TheAO,
  title={The activation of 5‐HT2A receptors in prefrontal cortex enhances dopaminergic activity},
  author={Anal{\'i}a Bortolozzi and Llorenç D{\'i}az-Mataix and Mar{\'i}a Cecilia Scorza and Pau Celada and Francesc Casa{\~n}as Artigas},
  journal={Journal of Neurochemistry},
  year={2005},
  volume={95}
}
Atypical antipsychotics show preferential 5‐HT2A versus dopamine (DA) D2 receptor affinity. At clinical doses, they fully occupy cortical 5‐HT2 receptors, which suggests a strong relationship with their therapeutic action. Half of the pyramidal neurones in the medial prefrontal cortex (mPFC) express 5‐HT2A receptors. Also, neurones excited through 5‐HT2A receptors project to the ventral tegmental area (VTA). We therefore hypothesized that prefrontal 5‐HT2A receptors can modulate DA transmission… 
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Involvement of 5-HT1A Receptors in Prefrontal Cortex in the Modulation of Dopaminergic Activity: Role in Atypical Antipsychotic Action
TLDR
The results suggest that the activation of mPFC 5-HT1A receptors enhances the activity of VTA DA neurons and mesocortical DA release, which may be involved in the elevation of extracellular DA produced by atypical antipsychotics.
Involvement of 5‐HT2A receptor and α2‐adrenoceptor blockade in the asenapine‐induced elevation of prefrontal cortical monoamine outflow
TLDR
It is proposed that low concentrations of asenapine in the mPFC exhibit a pharmacologically significant 5‐HT2A and α2 receptor antagonistic activity, which may contribute to enhance prefrontal monoamine release in vivo and, secondarily, its clinical effects in schizophrenia and bipolar disorder.
Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action
Stimulation of glutamate receptors in the ventral tegmental area is necessary for serotonin-2 receptor-induced increases in mesocortical dopamine release
The absence of 5-HT1A receptors has minor effects on dopamine but not serotonin release evoked by MK-801 in mice prefrontal cortex
TLDR
The lack of effect observed after the local MK-801 application suggests that the change in cortical monoamines is mainly driven by subcortical NMDA receptor blockade, without a significant involvement of PFC 5-HT1A receptors.
Dopamine release induced by atypical antipsychotics in prefrontal cortex requires 5-HT(1A) receptors but not 5-HT(2A) receptors.
TLDR
Results indicate that (1) 5-HT(1A)Rs are necessary for the APD-induced elevation in cortical DA transmission, and (2) this effect does not require 5- HT(2A)R blockade by APDs.
Dopamine and serotonin interactions in the prefrontal cortex: insights on antipsychotic drugs and their mechanism of action.
TLDR
It is concluded that although D2 receptor antagonism remains a critical factor in restoring impaired cortical activity, effects on 5-HT receptors may act in a synergistic manner on NMDA and GABA currents to potentiate antipsychotic actions in the PFC.
The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens
TLDR
It is argued that activation of 5-HT2C receptors on NAc shell, GABAergic, medium spiny neurons inhibits potassium Kv1.x channels, thereby enhancing inhibitory activity via intrinsic mechanisms and providing a potential reason for the non-addictive nature of classic hallucinogens.
5-HT2 receptors modulate the expression of antipsychotic-induced dopamine supersensitivity
Effects of S‐citalopram, citalopram, and R‐citalopram on the firing patterns of dopamine neurons in the ventral tegmental area, N‐methyl‐D‐aspartate receptor‐mediated transmission in the medial prefrontal cortex and cognitive function in the rat
TLDR
The data suggest that the excitatory effect of escitalopram on dopaminergic and NMDA receptor‐mediated neurotransmission may have bearing on its cognitive‐enhancing effect and superior efficacy compared to other SSRIs in major depression.
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