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

1 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. 2 Local administration of 5-OHi into the CA1 region of the rat hippocampus, via a microdialysis probe, significantly increased glutamate concentrations in the dialysates. 3 In rat hippocampal slices, using extracellular recordings in the CA1 region, 5-OHi (30-300 microM) increased the amplitude of population spikes and fEPSPs. 4 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 GABA(A)-mediated neurotransmission by increasing the frequency and the amplitude of pharmacologically isolated spontaneous inhibitory postsynaptic currents (sIPSC). 5 In separate experiments, performed by measuring AMPA or NMDA-induced depolarization in cortical wedges, 5-OHi did not modify glutamate receptor agonist responses. 6 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.