TY - JOUR
T1 - Electrophysiological evidence for a functional differentiation between subtypes of the 5-HT1 receptor
AU - Sinton, Christopher M.
AU - Fallon, Scott L.
PY - 1988/11/22
Y1 - 1988/11/22
N2 - 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.
AB - 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.
KW - 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin)
KW - CGS 12066
KW - Ipsapirone
KW - Raphe nuclei
KW - Substantia nigra
KW - TFMPP (trifluoromethylphenylpiperazine)
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U2 - 10.1016/0014-2999(88)90380-9
DO - 10.1016/0014-2999(88)90380-9
M3 - Article
C2 - 2906291
AN - SCOPUS:0023692293
SN - 0014-2999
VL - 157
SP - 173
EP - 181
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -