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Haigler HJ, Aghajanian GK. 
“Lysergic Acid Diethylamide and Serotonin: A-Comparison of Effects on Serotonergic Neurons and Neurons Receiving a Serotonergic Input”. 
J.Pharmacol.Exp.Ther.. 1974;188(3):688-99.
Abstract
The effects of lysergic acid diethylamide (LSD) and 5HT on central serotonergic neurons and those receiving a serotonergic input have been compared. Methods Halothane-anesthetised rats had the brain stem transected at the pretrigeminal level. 5 Barrel micropipettes (tips 4 and 5 pm) were filled with 2 M NaCl saturated with fast green, 5 M NaCl, D.05 M 5HT creatinine sulfate (Sigma), 0.001 M LSD and 0.2 M Ach (Calbiochem). Recordings of cells were of integrated unit rate and consisted of consecutive samples of 10 or 1 sec intervals of the analog output of an electronic counter. Recordings of cells were marked by deposition of fast green and the transport number of 5HT and LSD was determined. Cells in the amygdala, ventral lateral geniculate (VLG), the subiculum and the optic tectum, all of which receive projections from the raphe were tested for their response to microlontophoretic LSD and 5HT and i.v. LSD. For comparison, cells in the dorsal raphe nucleus (DRN) and cells with a-non-uniform or sparse input of 5HT terminals in the ventral hippocamp¨s (VH)-, thalamus, the dorsal lateral geniculate (DLG) and reticular formation were also tested. Cells in the 4 postsynaptic raphe areas were markedly less sensitive to LSD applied microiontophoretically than cells in the DRN. In the post-synaptic cells LSD produced only 50 0nhibition at 40 nA at doses 4 times larger than those causing total inhibition in the DRN. However, the sensitivity of post-synaptic and DRN cells to 5HT was about the same. In the VLG, 5HT blocked or red¨ced both background activity and the response to a light stimulus. Only the latter was blocked by LSD at low ejection - currents. When 20 mcg LSD was given i.v. (dose above that causing total inhibition of the raphe cells), there was an acceleration of firing- ˛f the postsynaptic cells, whilst subsequent 5HT (microiontophoretic) still inhibited them. To test the hypothesis that LSD indirectly inhibits raphe neurons by activating a neuronal feedback inhibitory system, a complete transection was made betweep the diencephalon and the mesencephalon. This failed to alter the above effects of i.v. LSD, VH and thalamic cells were unaffected by 5HT. LSD blocked or reduced eXcitatory responses in 7/8 cases. Many DLG cÚlls were readily inhibited by 5HT, but were relatively insensitive to LSD. In low doses LSD inhibits the firing of raphe cells by a direct action. LSD releases postsynaptic cells from a tonic raphe inhibition. The difference in sensitivity of the presynaptic and post - synaptic cells to LSD suggests that indoleamine receptors in the 2 areas have different steric req¨irements.
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