Two distinct serotonin receptors: regional variations in receptor binding in mammalian brain

Two distinct serotonin receptors in mammalian brain are labeled respectively with [³H]serotonin (5-HT₁) and [³H]spiperone (5-HT₂). In general, agonists display highest affinities for 5-HT₁ while antagonists prefer 5-HT₂ sites. To conduct regional studies of 5-HT receptors, we estimated 5-HT₂ sites with [³H]spiperone, using the 5-HT₂ specific antagonist cinanserin to displace binding to 5-HT₂ but not dopamine receptors and sulpiride to displace [³H]spiperone from dopamine but not 5-HT receptors. About 15% of cerebral cortical [³H]spiperone binding appears to involve dopamine sites and the remainder involves 5-HT₂ receptors. In the corpus striatum about 80% of [³H]spiperone binding labels dopamine receptors and the rest involves 5-HT₂ sites. [³H]mianserin binds about equally to 5-HT₂ sites are studies selectively by displacing histamine H₁-receptor binding with the H₁-antihistamine triprolidine. [³H]LSD labels both 5-HT₁ and 5-HT₂ receptors. Its binding to 5-HT₁ sites is displaced selectively with 5-HT, while its binding to 5-HT₂ receptors is displaced with cinanserin. [³H]5-HT labels only 5-HT₁ receptors. The regional distribution of the two 5-HT receptors is similar in rat, guinea pig and bovine brain. However, the regional patterns of 5-HT₁ and 5-HT₂ receptors differ considerably in all 3 species. The hippocampus is quite high in 5-HT₁ receptors but low in 5-HT₂ sites. The cerebellum contains the lowest levels of both 5-HT₁ and 5-HT₂ receptors. In bovine brain, most areas contain similar numbers of 5-HT₁ and 5-HT₂ receptors. However, the substantia nigra, the richest 5-HT₁ area inbovine brain, possesses 10 times more 5-HT₁ than 5-HT₂ sites.