Appel NM, Mitchell WM, Garlick RK, Glennon RA, Teitler M, De Souza EB.
“Autoradiographic Characterization of (±)- 1-(2 , 5-d imethoxy.-4-[125I]
Autoradgraphic Characterzation of (+)-1-(2,5-dimethoxy-4-[125I]iodophenyl)-2-aminopropane ([125I]DOI) Binding to 5-HT2 and 5-HT1c Receptors in Rat Brain”.
The Journal of Pharmacology and Experimental Therapeutics. 1990 Jul 19;255(2):843-57.
The 5-HT2 (serotonin) receptor has traditionally been labeled with antagonist radioligands such as [3H]ketanserin and [3H]spiperone, which label both agonist high-affinity (guanyl nucleotide-sensitive) and agonist low-affinity (guanyl nucleotide-insensitive) states of this receptor. The hallucinogen 1 -(2,5-dimethoxy-4- iodophenyi)-2-aminopropane (DOl) is an agonist which labels the high-affinity guanyl nucleotide-sensitive state of brain 5-HT2 receptors selectively. In the present study, conditions for autoradiographic
visualization of (±)-[‘25l]DOI-labeled 5-HT2 receptors were optimized and binding to slide-mounted sections was characterized with respect to pharmacology, guanyi nucleotide sensitivity and anatomical distribution. In slide-mounted rat brain sections(±)-[125I]DOI binding was saturable, of high affinity (KD ̴4nM) and displayed a pharmacologic profile typical of 5-HT2 receptors. Consistent with coupling of 5-HT2 receptors in the high-affinity state to a guanyl nudeotide regulatory protein, [125lJD0l binding was inhibited by guanyl nudeotides but not by adenosine triphosphate. Patterns of autoradiographic distribution of  DOl binding to 5-HT2 receptors were similar to those seen with [3H]ketansenn- and [125l]-iysergic acid diethylamide-labeled 5- HT2 receptors. However, the density of 5-HT2 receptors labeled by the agonist [125l]DOl was markedly lower (30-50%) than that labeled by the antagonist [3H]ketansenn. High densities of [125l]DOl labeling were present in olfactory bulb, anterior regions of
cerebral cortex (layer IV), claustrum, caudate putamen, globus pallidus, ventral pallidum, islands of Calleja, mammillary nuclei and inferior olive. Binding in hippocampus, thalamus and hypethalamus was generally sparse. Of note, choroid plexus, a site rich in 5-HT1c receptors had a high density of [125l]DOl binding sites but [3H]ketansenn binding in this region was low. Studies in which [125l]DOl binding to 5-HT2 receptors was blocked with
spiperone revealed persisting robust [125l]DOl binding in choroid plexus, which was guanyl nucleotide-sensitive and displayed a pharmacologic profile consistent with its binding to 5-HT1c receptors. These studies suggest that [125l]DOl may be useful as a
radiolabel for visualizing the agonist high-affinity state of 5-HT2 receptors and for visualizing 5-HT1c receptors.