The presence of 5-HT in the cortical regions is to increase postsynaptic potentials. 5-HT2A receptors induced activation in the pyramidal cells of the neocortex, having an excitatory effect rather than the previously thought of inhibitory effect. 

University of South Florida

Neuronal Actions of Hallucinogenic Drugs

Aghajanian, G., Marek, G. Serotonin and Hallucinogens. Neuropsychopharmacol 21, 16–23 (1999). https://doi.org/10.1016/S0893-133X(98)00135-3

Serotonin and Hallucinogens

LSD was found to have a potent inhibitory effect upon tonically firing 5-HT neurons in the raphe nucleus. Inhibition was observed through direct action in the somatodendritic region of 5-HT neurons. Indoleamines have also been seen to inhibit these serotonin neurons in the same nuclei. LSD is potent in its agonist abilities at the 5-HT1A autoreceptors accounting for inhibitory effects on Raphe Neurons. It was seen that mescaline and phenethylamines don't have an affinity for these receptors. The actions of LSD are similar to other drugs, like buspirone,  known to have anxiolytic effects.

Effect of Hallucinogens on 5-HT Neurons of Raphe Nuclei

It has been shown that there is a great affinity between the indoleamines and phenethylamine hallucinogens for 5-HT2 receptors. These receptors are not located presynaptically, often seen in different regions of the brain.

Affinity for 5-HT2 receptors vorrelates with hallucinogenic Potency

Hallucinogens have produced a paradoxical facilitation of the activation of LC neurons, not through direct action as it cannot be mimicked. The effects can be reversed with low doses of 5-HT2 antagonists or antipsychotics.

Hallucinogens enhance sensory responses in the Locus Coeruleus vida 5-HT2A receptors

5-HT2A receptors enhance glutamate release in the Neocortex

Experiments suggest that 5-HT induces EPSCs in the neocortical cells via focal mechanism not requiring impulse flow.
1. Rarely are any neurons induced by the application of 5-HT
2. none of the pyramidal cells were depolarised by 5-HT
3. There were no cells detected to be firing extracellularly through Microiontophoretic electrode.

A focal Mechanism for 5-HT2A induced glutamate release onto apical denndrites of layer V pyramidal cells

This study has shown that, as well as synchronous release, there is an asynchronous release characterized by the presence of EPSCs with a longer latency than what was seen the other type of release. This can happen with the residue of calcium in the terminals. It was found that LSD and other hallucinogens promote this interactions. 

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