The distribution of serotonin-2 (5-HT2) receptors in the rat brain was studied by
light microscopic quantitative autoradiography. Receptors were labeled with four ligands:
[3H]ketanserin, [3H]mesulergine, [3H]LSD and [3H]spiperone, which are reported to
show high affinity for 5-HT2 receptors. Co-incubation with increasing concentrations
of several well-known 5-HT2-selective drugs, such as pirenperone, cinanserin and ketanserin,
resulted in an inhibition of the binding of the four 3H-labeled ligands to the same
areas. However, all of them recognized, in addition to 5-HT2 sites, other populations
of binding sites. Receptor densities were quantified by microdensitometry with the
aid of a computer-assisted image-analysis system. Our results reveal a heterogeneous
distribution of 5-HT2 receptor densities in the rat brain. Very high concentrations
were localized in the claustrum, olfactory tubercle and layer IV of the neocortex.
The anterior olfactory nucleus, piriform cortex and layer I of neocortex were also
rich in 5-HT2 receptors. Intermediate concentrations of receptors were found in caudate
putamen, nucleus accumbens, layer V of neocortex, ventral dentate gyrus and mammillary
bodies. Areas containing only low concentrations of receptors included the thalamus,
hippocampus, brainstem, medulla, cerebellum and spinal cord. The specificity of the
different ligands used is discussed in terms of the other populations of sites recognized
by them. The distribution of 5-HT2 receptors here reported is discussed in correlation
with (a) the known distribution of serotoninergic terminals, (b) the specific anatomical
systems and (c) the central effects reported to be mediated by 5-HT2-selective drugs.