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

Stephen J. Peroutka, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)339-347
Number of pages9
JournalBrain research
Volume208
Issue number2
DOIs
StatePublished - Mar 16 1981

Keywords

  • d-lysergic acid diethylamide
  • histamine H receptors
  • mianserin
  • serotonin
  • spiperone

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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