Electrophysiological studies on oxindole, a neurodepressant tryptophan metabolite

1 The aim of the present work was to investigate the electrophysiological e ffects of oxindole, a tryptophan metabolite present in rat blood and brain, and recently proposed as a contributing factor in the pathogenesis of hepa tic encephalopathy. 2 Using rat hippocampal slices in vitro and extra- or intracellular recordi ngs, we evaluated oxindole effects on the neurotransmission of the CA1 regi on following orthodromic stimulation of the Schaffer collaterals. 3 Oxindole (0.3-3 mM) decreased the amplitude of population spikes extracel lularly recorded at the somatic level and of the fEPSPs recorded at the den dritic level. In intracellular recordings, oxindole (0.1-3 mM) did not affe ct the resting membrane potential or the neuronal input resistance, but red uced the probability of firing action potentials upon either synaptic or di rect activation of the pyramidal cells. 4 Oxindole (0.3-3 mM) increased the threshold and the latency of firing act ion potentials elicited by depolarizing steps without changing the duration or the peak amplitude of the spikes. It also significantly increased the s pike frequency adaptation induced by long lasting (400 ms) depolarizing sti muli. 5 In separate experiments, performed by measuring AMPA or NMDA-induced resp onses in cortical slices, oxindole (1-3 mM) did not modify glutamate recept or agonist responses. 6 Our results show that concentrations of oxindole which may be reached in pathological conditions, significantly decrease neuronal excitability by mo difying the threshold of action potential generation.