Autoradiography of LSD and 2,5-dimethoxyphenylisopropylamine psychotomimetics demonstrates regional, specific cross-displacement in the rat brain.

We previously reported the autoradiographic localization of specific, high-affinity binding sites for R-(-)-4-[125I]-2,5-dimethoxyphenylisopropylamine (125I-DOI), a new psychotomimetic radioligand, in the rat brain (McKenna et al., 1987). DOI and its 4-brominated and 4-alkylated congeners (DOB, DOM and DOET) are potent hallucinogenic agents in humans. [3H]DOB has recently been characterized as an agonist that selectively labels a guanylate-sensitive high-affinity state of the 5HT 2 receptor (Lyon et al., 1987). Our previous results support these findings by consistently showing the highest binding densities in regions that a previous autoradiographic study, utilizing radio-iodine-labeled LSD (125I-LSD), characterized as containing high densities of 5HT 2 receptors (Nakada et al., 1984). In the present study, we report that two psychotomimetic ligands, LSD and the halogenated phenylalkylamine DOB, mutually and specifically cross-displace azSI-LSD and 125I-DOI in specific brain regions. Incubation of rat forebrain sections in 200 pM 125I-LSD (fig. 1A) gave high binding values in several brain regions. The binding values (expressed in units of fmol/mg protein _+ S.E.) in each region were as follows: nucleus acumbens