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.
Partridge
L D
LD
Department of Neurosciences, University of New Mexico, School of Medicine, Albuquerque, NM 87131, USA. dpartridge@salud.unm.edu
Valenzuela
C F
CF
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