Loading…

5‐hydroxyindole causes convulsions and increases transmitter release in the CA1 region of the rat hippocampus

5‐hydroxyindole (5‐OHi) is a proposed tryptophan metabolite able to cause convulsions when systemically injected into rodents. We studied its effects using microdialysis in vivo and electrophysiological approaches in vitro. Local administration of 5‐OHi into the CA1 region of the rat hippocampus, vi...

Full description

Saved in:
Bibliographic Details
Published in:British journal of pharmacology 2003-01, Vol.138 (1), p.245-253
Main Authors: Mannaioni, Guido, Carpenedo, Raffaella, Moroni, Flavio
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:5‐hydroxyindole (5‐OHi) is a proposed tryptophan metabolite able to cause convulsions when systemically injected into rodents. We studied its effects using microdialysis in vivo and electrophysiological approaches in vitro. Local administration of 5‐OHi into the CA1 region of the rat hippocampus, via a microdialysis probe, significantly increased glutamate concentrations in the dialysates. In rat hippocampal slices, using extracellular recordings in the CA1 region, 5‐OHi (30–300 μM) increased the amplitude of population spikes and fEPSPs. In the same preparation, using intracellular recordings in CA1 pyramidal neurons, 5‐OHi reduced the latency of firing induced by direct depolarization and increased both evoked excitatory and slow inhibitory postsynaptic potential amplitudes, without affecting the resting membrane potential, the after‐hyperpolarization or the neuronal input resistance. It also altered GABAA‐mediated neurotransmission by increasing the frequency and the amplitude of pharmacologically isolated spontaneous inhibitory postsynaptic currents (sIPSC). In separate experiments, performed by measuring AMPA or NMDA‐induced depolarization in cortical wedges, 5‐OHi did not modify glutamate receptor agonist responses. Our results show that 5‐OHi causes convulsions, modifies the properties and the function of the hippocampal circuitry, and facilitates the output of both excitatory and inhibitory transmitters. British Journal of Pharmacology (2003) 138, 245–253. doi:10.1038/sj.bjp.0705007
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0705007