PMID: 8943785Sep 1, 1996Paper

Potentiation by dehydroepiandrosterone of the neuronal response to N-methyl-D-aspartate in the CA3 region of the rat dorsal hippocampus: an effect mediated via sigma receptors

The Journal of Endocrinology
G DebonnelC de Montigny

Abstract

We have previously shown in vivo that low doses of selective sigma (sigma) receptor ligands potentiate selectively and dose-dependently the excitatory response of pyramidal neurons to microiontophoretic applications of N-methyl-D-aspartate (NMDA) in the CA3 region of the rat dorsal hippocampus. As several neuroactive steroids such as progesterone and testosterone have a high affinity for sigma receptors, the effects of some neuroactive steroids on the NMDA-induced neuronal response were assessed using extracellular unitary recordings of CA3 dorsal hippocampus pyramidal neurons obtained in anesthetized Sprague-Dawley rats. Low doses of dehydroepiandrosterone (DHEA) potentiated selectively and dose-dependently the NMDA response without affecting those to acetylcholine or quisqualate. This potentiating effect of DHEA was suppressed by the selective sigma 1 antagonist NE-100 and by the non-selective sigma antagonist haloperidol. Low doses of progesterone and of testosterone did not modify the NMDA response, but reversed the potentiating effects of DHEA as well as those of the non-steroidal sigma ligands di-tolylguanidine (DTG), (+)pentazocine and JO-1784. The two neuroactive steroids with a low affinity for sigma receptors, pregnen...Continue Reading

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