Neurosteroid-induced enhancement of glutamate transmission in rat hippocampal slices.
Pregnenolone sulfate, one of the most abundantly produced neurosteroids in the hippocampus, has well characterized effects at postsynaptic receptors including the N-methyl-D-asparate type of glutamate receptor. Little is known, however, about the mechanism of action of neurosteroids on the release of glutamate. In this study we describe a robust effect of pregnenolone sulfate at glutamatergic synapses in the CA1 region of the hippocampus. In particular, we found that pregnenolone sulfate enhances paired-pulse facilitation of EPSPs at the two major classes of ionotropic glutamate receptors with an EC(50)<1 microM. Thus, we propose a novel mechanism of action of neurosteroids in hippocampal neurons that involves the modulation of glutamate release.
Department of Neurosciences, University of New Mexico, School of Medicine, Albuquerque, NM 87131, USA. dpartridge@salud.unm.edu
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Partridge
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Valenzuela
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D009924:Organ Culture Techniques; D011284:Pregnenolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C018370:pregnenolone sulfate; D018698:Glutamic Acid; D011284:Pregnenolone