Serotonin receptors in hippocampus and frontal cortex.

The inhibition by various serotonin agonists and antagonists of the binding of 3 nM 3H-d-LSD, 1.7 nM 3H-serotonin and 0.22 nM 3H-spiperone to homogenates of calf hippocampus and frontal cortex was studied. The 50% inhibitory concentration (IC50) for these drugs versus 3H-d-LSD binding had similar values to and correlated with corresponding IC50 values versus 3H-serotonin binding in the hippocampus, suggesting that 3H-LSD and 3H-serotonin label similar sites in this region. In the calf frontal cortex, serotonin revealed a biphasic inhibition against 3H-d-LSD binding and the tryptamines inhibited over a concentration range of 10 000-fold. The IC25 values of various drugs versus 3H-d-LSD binding correlated with the IC50 values versus 3H-serotonin, but did not correlate with the IC50 values versus 3H-spiperone. These data suggest that 3H-d-LSD bound to more than one serotonin site in the calf frontal cortex and that 3H-spiperone bound to a separate serotonergic site. Scatchard analyses of the binding for these three 3H-ligands indicated that in the calf frontal cortex the density of 3H-d-LSD sites was approximately equal to the sum of the densities for 3H-serotonin (S-1 sites) and 3H-spiperone (S-2 sites). Two weeks after serotonin-depleting radiofrequency heat lesions of the midbrain dorsal and median raphe nuclei in rats, both 3H-serotonin and 3H-LSD showed enhanced binding in the hippocampus. These data support previous suggestions that supersensitivity develops specifically in serotonin receptors following afferent denervation.