Groundbreaking work on the effects of serotonin (6) and hallucinogenic drugs on nerve cells
has been done in the group of George K. Aghajanian at Yale University, USA, using neurophysiological
methods on brain slice preparations. They showed profound effects of serotonin
(6), LSD (12), and DOI (10) on the firing rate of pyramidal cells in layer V of the medial
prefrontal cortex (mPFC). Serotonin (6) applied to cortical brain slices resulted in a strong
increase in spontaneous pyramidal cell firing. This effect was stronger in the medial prefrontal
cortex compared to other cortical regions while in subcortical regions 5-HT (6) even had
inhibitory effects. Serotonin (6) applied in close proximity to the dendrites of the pyramidal
cells dramatically increased their firing rate after several seconds. This effect was most pronounced
in layer IV/Va in a dendritic region close to the cell body, but still observable in layer
I/II, a more distant dendritic region. Application 100 - 200 µm away from the vertical dendrites
did not result in activation. Also application onto the pyramidal cell body in layer Vb or into
the basilar dendritic field in layer Vb/VI below the cell body did not result in increased firing [7].
The pyramidal firing in the experiments above was mediated by 5-HT2A receptors as shown
by antagonist experiments. However, 5-HT2A receptor activation did not cause a pronounced
membrane depolarization and therefore could not directly induce firing of pyramidal cells
