DETAILED MAPPING OF SEROTONIN 5-HT1B AND 5-HT1D RECEPTOR MESSENGER-RNA AND LIGAND-BINDING SITES IN GUINEA-PIG BRAIN AND TRIGEMINAL GANGLION- CLUES FOR FUNCTION

The similar pharmacology of the 5-HT1B and 5-HT1D receptors, and the l ack of selective compounds sufficiently distinguishing between the two receptor subtypes, have hampered functional studies on these receptor s. In order to provide clues for differential functional roles of the two subtypes, we performed a parallel localization study throughout th e guinea-pig brain and the trigeminal ganglia by means of quantitative in situ hybridization histochemistry (using [S-35]-labelled riboprobe s probes for receptor messenger RNA) and receptor autoradiography (usi ng a new radioligand [H-3]alniditan). The anatomical patterns of 5-HT1 B and 5-HT1D receptor messenger RNA were quite different. While 5-HT1B receptor messenger RNA was abundant throughout the brain (with highes t levels in the striatum, nucleus accumbens, olfactory tubercle, corte x, hypothalamus, hippocampal formation, amygdala, thalamus, dorsal rap he and cerebellum), 5-HT1D receptor messenger RNA exhibited a more res tricted pattern; it was found mainly in the olfactory tubercle, entorh inal cortex, dorsal raphe, cerebellum, mesencephalic trigeminal nucleu s and in the trigeminal ganglion. The density of 5-HT1B/1D binding sit es (combined) obtained with [H-3]alniditan autoradiography was high in the substantia nigra, superior colliculus and globus pallidus, wherea s lower levels were detected in the caudate-putamen, hypothalamus, hip pocampal formation, amygdala, thalamus and central gray. This distribu tion pattern was indistinguishable from specific 5-HT1B receptor label ling in the presence of ketanserin under conditions to occlude 5-HT1D receptor labelling; hence the latter were below detection level. Relat ionships between the regional distributions of the receptor messenger RNAs and binding sites and particular neuroanatomical pathways are dis cussed with respect to possible functional roles of the 5-HT1B and 5-H T1D receptors. (C) 1997 IBRO. Published by Elsevier Science Ltd.