5.HT1 receptors in the vertebrate brain. Regional distribution examined by autoradiography.
The regional distribution of high affinity [3H]5-HT recognition sites in the brain of several vertebrates (pigeon, rat, mouse, guinea-pig, cat, dog, monkey and human) was analyzed using in vitro autoradiography. The presence of subtypes of 5-HT1 binding sites was investigated by selective displacements with 8-OH-DPAT, mesulergine and (+/-)SDZ 21-009 at appropriate concentrations to block 5-HT1A, 5-HT1C and 5-HT1B sites respectively. In addition, 5-HT1A and 5-HT1C sites were directly visualized with the more selective radioligands [3H]8-OH-DPAT and [3H]mesulergine, respectively. In the pigeon brain, total [3H]5-HT binding sites were enriched in all telencephalic areas. Densely labelled regions were also present in the optic tectum and the brainstem. No binding was observed in the cerebellum. 8-OH-DPAT and mesulergine only displaced a small proportion of [3H]5-HT binding in most of the areas where high concentrations of 5-HT1 sites were found. (+/-)SDZ 21-009 did not affect [3H]5-HT binding in the regions examined. Taking into account our pharmacological studies, these results suggest that the majority of 5-HT1 sites belong to the 5-HT1D subtype in the pigeon brain. In the mammalian species investigated high levels of [3H]5-HT binding were found in the neo-cortex, hippocampal formation, basal ganglia and related structures (substantia nigra), raphe dorsalis, nucleus superior colliculus and choroid plexus. However, these brain areas were differentially enriched in subtypes of 5-HT1 recognition sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Waeber
C
C
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Dietl
M M
MM
Hoyer
D
D
Palacios
J M
JM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000368:Aged; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure*; D002415:Cats; D004195:Disease Models, Animal; D004285:Dogs; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009069:Movement Disorders / Q000378:metabolism; D011985:Receptors, Serotonin / Q000145:classification* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014316:Tritium
D004873:Ergolines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D014316:Tritium; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C031649:mesulergine