Electrophysiological evidence for a functional differentiation between subtypes of the 5-HT1 receptor.
Serotonin (5-HT) neurons in the dorsal (DRN) and median (MRN) raphe nuclei, and dopamine (DA) neurons in the substantia nigra (SN) were recorded extracellularly in the anesthetized rat. Compounds which have a relatively high affinity for the 5-HT1A or 5-HT1B subtypes of the 5-HT1 receptor were administered and their effect on the firing rate of the monoamine cells was determined. 5-HT1A ligands were more potent in inhibiting impulse activity in the DRN than in the MRN, but had little effect in the SN. In contrast, 5-HT1B ligands increased the firing rate of MRN 5-HT units at low doses, and were also effective inhibitors of DA cell firing in the SN. These results could be correlated with recently described differences in the distribution of the 5-HT1A and 5-HT1B receptor subtypes, and were interpreted as indicating possible functional differentiation between these subtypes. In particular, agonist activity at the 5-HT1B autoreceptor site may decrease 5-HT release, suggesting a presynaptic locus for this receptor in the somatodendritic region. The site also appears to be implicated in 5-HT modulation of nigral DA impulse flow.
Sinton
C M
CM
Research Department, Ciba-Geigy Corporation, Summit, NJ 07901.
Fallon
S L
SL
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D010879:Piperazines; D011743:Pyrimidines; D011810:Quinoxalines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C052561:CGS 12066B; C018406:1-(3-trifluoromethylphenyl)piperazine; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin