Endogenous serotonin inhibits epileptiform activity in rat hippocampal CA1 neurons via 5-hydroxytryptamine(1A) receptor activation

K. T. Lu, Po-Wu Gean

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

The modulatory effects of endogenous serotonin on the synaptic transmission and epileptiform activity were studied in the rat hippocampus with the use of extracellular and intracellular recording techniques. Field excitatory postsynaptic potential was reversibly depressed by serotonin in a concentration-dependent manner. Intracellular recordings revealed that serotonin-mediated synaptic depression was unaffected by extracellular Ba2+ or intracellular application of Cs+ while the postsynaptic hyperpolarizing effect was completely blocked. Epileptiform activity induced by picrotoxin (50 μM), a GABA(A) receptor antagonist, was also dose-dependently suppressed by serotonin. The antiepileptic effect was mimicked by 5- hydroxytryptamine(1A) agonist and was blocked by 5-hydroxytryptamine(1A) antagonists. 5-Hydroxytryptamine2 antagonist had no effect on the modulation. Similarly, fluoxetine, a selective serotonin re-uptake blocker, potently inhibited the epileptiform activity and this effect was blocked by 5-hydroxytryptamine(1A) receptor antagonist. Depletion of endogenous serotonin by pretreating the slices with p-chloroamphetamine completely prevented the antiepileptic action of fluoxetine, without modifying the action of serotonin in the same cells. These results suggest that the antiepileptic action of fluoxetine is due to an enhancement of endogenous serotonin which in turn is mediated by 5-hydroxytryptamine(1A) receptor. Endogenous serotonin transmission in the hippocampus is therefore capable of limiting the development and propagation of seizure activity.

Original languageEnglish
Pages (from-to)729-737
Number of pages9
JournalNeuroscience
Volume86
Issue number3
DOIs
Publication statusPublished - 1998 Jun 8

Fingerprint

Receptor, Serotonin, 5-HT1A
Serotonin
Neurons
Fluoxetine
Anticonvulsants
Hippocampus
p-Chloroamphetamine
GABA-A Receptor Antagonists
Serotonin Receptor Agonists
Picrotoxin
Serotonin Antagonists
Excitatory Postsynaptic Potentials
Synaptic Transmission
Seizures

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

@article{00e60604b2794f5c9cdb675d51d0c1a0,
title = "Endogenous serotonin inhibits epileptiform activity in rat hippocampal CA1 neurons via 5-hydroxytryptamine(1A) receptor activation",
abstract = "The modulatory effects of endogenous serotonin on the synaptic transmission and epileptiform activity were studied in the rat hippocampus with the use of extracellular and intracellular recording techniques. Field excitatory postsynaptic potential was reversibly depressed by serotonin in a concentration-dependent manner. Intracellular recordings revealed that serotonin-mediated synaptic depression was unaffected by extracellular Ba2+ or intracellular application of Cs+ while the postsynaptic hyperpolarizing effect was completely blocked. Epileptiform activity induced by picrotoxin (50 μM), a GABA(A) receptor antagonist, was also dose-dependently suppressed by serotonin. The antiepileptic effect was mimicked by 5- hydroxytryptamine(1A) agonist and was blocked by 5-hydroxytryptamine(1A) antagonists. 5-Hydroxytryptamine2 antagonist had no effect on the modulation. Similarly, fluoxetine, a selective serotonin re-uptake blocker, potently inhibited the epileptiform activity and this effect was blocked by 5-hydroxytryptamine(1A) receptor antagonist. Depletion of endogenous serotonin by pretreating the slices with p-chloroamphetamine completely prevented the antiepileptic action of fluoxetine, without modifying the action of serotonin in the same cells. These results suggest that the antiepileptic action of fluoxetine is due to an enhancement of endogenous serotonin which in turn is mediated by 5-hydroxytryptamine(1A) receptor. Endogenous serotonin transmission in the hippocampus is therefore capable of limiting the development and propagation of seizure activity.",
author = "Lu, {K. T.} and Po-Wu Gean",
year = "1998",
month = "6",
day = "8",
doi = "10.1016/S0306-4522(98)00106-7",
language = "English",
volume = "86",
pages = "729--737",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "3",

}

Endogenous serotonin inhibits epileptiform activity in rat hippocampal CA1 neurons via 5-hydroxytryptamine(1A) receptor activation. / Lu, K. T.; Gean, Po-Wu.

In: Neuroscience, Vol. 86, No. 3, 08.06.1998, p. 729-737.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Endogenous serotonin inhibits epileptiform activity in rat hippocampal CA1 neurons via 5-hydroxytryptamine(1A) receptor activation

AU - Lu, K. T.

AU - Gean, Po-Wu

PY - 1998/6/8

Y1 - 1998/6/8

N2 - The modulatory effects of endogenous serotonin on the synaptic transmission and epileptiform activity were studied in the rat hippocampus with the use of extracellular and intracellular recording techniques. Field excitatory postsynaptic potential was reversibly depressed by serotonin in a concentration-dependent manner. Intracellular recordings revealed that serotonin-mediated synaptic depression was unaffected by extracellular Ba2+ or intracellular application of Cs+ while the postsynaptic hyperpolarizing effect was completely blocked. Epileptiform activity induced by picrotoxin (50 μM), a GABA(A) receptor antagonist, was also dose-dependently suppressed by serotonin. The antiepileptic effect was mimicked by 5- hydroxytryptamine(1A) agonist and was blocked by 5-hydroxytryptamine(1A) antagonists. 5-Hydroxytryptamine2 antagonist had no effect on the modulation. Similarly, fluoxetine, a selective serotonin re-uptake blocker, potently inhibited the epileptiform activity and this effect was blocked by 5-hydroxytryptamine(1A) receptor antagonist. Depletion of endogenous serotonin by pretreating the slices with p-chloroamphetamine completely prevented the antiepileptic action of fluoxetine, without modifying the action of serotonin in the same cells. These results suggest that the antiepileptic action of fluoxetine is due to an enhancement of endogenous serotonin which in turn is mediated by 5-hydroxytryptamine(1A) receptor. Endogenous serotonin transmission in the hippocampus is therefore capable of limiting the development and propagation of seizure activity.

AB - The modulatory effects of endogenous serotonin on the synaptic transmission and epileptiform activity were studied in the rat hippocampus with the use of extracellular and intracellular recording techniques. Field excitatory postsynaptic potential was reversibly depressed by serotonin in a concentration-dependent manner. Intracellular recordings revealed that serotonin-mediated synaptic depression was unaffected by extracellular Ba2+ or intracellular application of Cs+ while the postsynaptic hyperpolarizing effect was completely blocked. Epileptiform activity induced by picrotoxin (50 μM), a GABA(A) receptor antagonist, was also dose-dependently suppressed by serotonin. The antiepileptic effect was mimicked by 5- hydroxytryptamine(1A) agonist and was blocked by 5-hydroxytryptamine(1A) antagonists. 5-Hydroxytryptamine2 antagonist had no effect on the modulation. Similarly, fluoxetine, a selective serotonin re-uptake blocker, potently inhibited the epileptiform activity and this effect was blocked by 5-hydroxytryptamine(1A) receptor antagonist. Depletion of endogenous serotonin by pretreating the slices with p-chloroamphetamine completely prevented the antiepileptic action of fluoxetine, without modifying the action of serotonin in the same cells. These results suggest that the antiepileptic action of fluoxetine is due to an enhancement of endogenous serotonin which in turn is mediated by 5-hydroxytryptamine(1A) receptor. Endogenous serotonin transmission in the hippocampus is therefore capable of limiting the development and propagation of seizure activity.

UR - http://www.scopus.com/inward/record.url?scp=0031806840&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031806840&partnerID=8YFLogxK

U2 - 10.1016/S0306-4522(98)00106-7

DO - 10.1016/S0306-4522(98)00106-7

M3 - Article

VL - 86

SP - 729

EP - 737

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 3

ER -